11
Case#: Patient 11 (see Table 2), 33 weeks (Gestational age)
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.653T>C (p.L218P)
Variant1ClinVarID: 222995
Variant1CAID: CA:356986
Variant2: c.653T>C (p.L218P)
Variant2ClinVarID: 222995
Variant2CAID: CA:356986
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
4
Case#: Patient 4 (see Table 2), 39 weeks, 6 days (Gestational age)
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Upper respiratory tract involvement
CaseNotHPOs: Inguinal hernia (HP:0000023)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0.25 nmol x mg-1 × hr-1
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1205G>A (p.W402X)
Variant2ClinVarID: 11908
Variant2CAID: CA220498
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
p.E274X [37]
This paper references a pt from PMID: 12865757 which can no longer be accessed. Links/DOI say they're no longer found.
253
Case#: Patient 23 (see Table 2), 40 weeks (Gestational age)
DiseaseAssertion: MPS1-S
FamilyInfo: Sibling of Patient 26 (see Table 2)
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 1.17 nmol x mg-1 × hr-1
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.208C>T (p.Q70X)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2: c.1148G>A (p.R383H)
Variant2ClinVarID: 558189
Variant2CAID: CA:2802205
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
232
Case#: Patient 23 (see Table 2), 37 weeks (Gestational age)
DiseaseAssertion: MPS1-H/S
FamilyInfo: Homozygous twin of Patient 22 (see Table 2)
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: Inguinal hernia (HP:0000023)
CaseNotHPOFreeText: Upper respiratory tract involvement
CaseEnzymeAssay: 2.43 nmol x mg-1 × hr-1
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1598C>G (p.P533R)
Variant1ClinVarID: 11910
Variant1CAID: CA256112
Variant2: c.1598C>G (p.P533R)
Variant2ClinVarID: 11910
Variant2CAID: CA256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
16
Case#: Patient 16 (see Table 2), Gestational age unavailable
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0.32 nmol x mg-1 × hr-1
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: (p.H425fs) - unknown what the protein change is due to the frameshift
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: (p.H425fs) - unknown what the protein change is due to the frameshift
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
c.659G > A
Case#: No additional case information provided
DiseaseAssertion: MPSI-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.659G>A (p.G220D)
Variant1ClinVarID: 3384858
Variant1CAID: CA355962012
Variant2: c.979G>C (p.A327P)
Variant2ClinVarID: 167190
Variant2CAID: CA234128
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
c.1898C > A
Case#: No additional case information provided
DiseaseAssertion: MPSI-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0.13 umol/g hr, reference range 10–50 umol/g hr.
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1898C>A (p.S633X)
Variant1ClinVarID: 1068474
Variant1CAID: CA355966009
Variant2: c.208C>T (p.Q70X)
Variant2ClinVarID: 11909
Variant2CAID: CA204563
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
c.1456G > T
Case#: No additional case information provided
DiseaseAssertion: MPSI-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1456G>T (p.E486X)
Variant1ClinVarID: 651168
Variant1CAID: CA355964628
Variant2: c.1456G>T (p.E486X)
Variant2ClinVarID: 651168
Variant2CAID: CA355964628
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Patient 2 was diagnosed with Hurler syndrome at two and a half years of age. Symptoms included coarse facies, cloudy cornea, claw-hand deformity, hepatosplenomegaly, hearing loss and mental retardation.
Case#: Cairns Patient 2, Thai, 2.5yo at dx
DiseaseAssertion: Hurler syndrome, MPS1
FamilyInfo:
CasePresentingHPOs: HP:0007957, HP:0000280, HP:0001433, HP:0000365, HP:0001249, HP:0034337
CaseHPOFreeText: The activity of leukocyte cc-iduronidase in both patients was not detectable (< 10 nmol/ mg/18 h)
CaseNotHPOs:
CaseNotHPOFreeText:
GenotypingMethod: PCR amplification of cDNA and genomic coding regions of the α-L-iduronidase gene and direct sequencing
PreviouslyPublished: n/a
Variant: c.895G>T (p.Glu299Ter); c.252insertC
CAID: CA355962511; CA355945969
SupplementalData: n/a
53/F
Case#: Patient 53, female, Han origin, 4 years old (age at diagnosis)
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)
CaseHPOFreeText: Cardiac disease
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA activity 0.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.
CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.236C>T (p.A79V)
Variant1ClinVarID: 1458769
Variant1CAID: CA356987
Variant2: c.1402+1G>T
Variant2ClinVarID: 1323099
Variant2CAID: CA355964387
AdditionalVariants: N/A
ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.
PreviouslyPublished N/A
48/M
Case#: Patient 48, male, Han origin, 19 months old (age at diagnosis)
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)
CaseHPOFreeText: Cardiac disease
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA activity 1.5 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.
CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.536C>G (p.T179R)
Variant1ClinVarID: 556358
Variant1CAID: CA355961718
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
51/F
Case#: Patient 51, female, Han origin, 1 year 6 months old (age at diagnosis)
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)
CaseHPOFreeText: Cardiac disease
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA activity 0.4 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.
CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.46_57del12 (p.Ser16_Ala19del)
Variant1ClinVarID: 92643
Variant1CAID: CA220509
Variant2: c.792+1G>C
Variant2ClinVarID: N/A
Variant2CAID: CA355962280
AdditionalVariants: N/A
ParentalGenotype: Father - c.46-57del12, Mother - c.792+1G>C. The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.
PreviouslyPublished N/A
8/M
Case#: Patient 8, male, Han origin, 6 years old (age at diagnosis)
DiseaseAssertion: MPS1-H/S
FamilyInfo: N/A
CasePresentingHPOs: Macrocephaly, Joint stiffness, Hepatosplenomegaly, Airway obstruction (HP:0000256, HP:0001387, HP:0001433, HP:0006536)
CaseHPOFreeText: N/A
CaseNotHPOs: Global Developmental Delay, Mongolian macula, Hernia (HP:0001263, HP:0011369, HP:0100790)
CaseNotHPOFreeText: Cardiac disease
CaseEnzymeAssay: IDUA activity 0.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.
CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1037T>G (p.L346R)
Variant1ClinVarID: 11927
Variant1CAID: CA256128
Variant2: c.1402+2T>G
Variant2ClinVarID: 553131
Variant2CAID: CA355964392
AdditionalVariants: N/A
ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.
PreviouslyPublished N/A
46/M
Case#: Patient 46, male, Han origin, 9 years 6 months old (age at diagnosis)
DiseaseAssertion: MPS1-H/S
FamilyInfo: N/A
CasePresentingHPOs: Joint stiffness, Hernia (HP:0001387, HP:0100790)
CaseHPOFreeText: N/A
CaseNotHPOs: Global Developmental Delay, Macrocephaly, Mongolian macula, Hepatosplenomegaly, Airway obstruction (HP:0001263, HP:0000256, HP:0011369, HP:0001433, HP:0006536)
CaseNotHPOFreeText: Cardiac disease
CaseEnzymeAssay: IDUA activity 1.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.
CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.532G>A (p.E178K)
Variant1ClinVarID: 2203495
Variant1CAID: 355961709
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
15/M
Case#: Patient 15, male, Han origin, 6 years old (age at diagnosis)
DiseaseAssertion: MPS1-H/S
FamilyInfo: N/A
CasePresentingHPOs: Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)
CaseHPOFreeText: N/A
CaseNotHPOs: Global Developmental Delay (HP:0001263)
CaseNotHPOFreeText: Cardiac disease
CaseEnzymeAssay: IDUA activity 1.4 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.
CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.349delT (p.Tyr117ThrfsTer16)
Variant1ClinVarID: 1451219
Variant1CAID: CA2573137553
Variant2: c.1898C>T (p.S633L)
Variant2ClinVarID: 556406
Variant2CAID: CA355966010
AdditionalVariants: N/A
ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.
PreviouslyPublished N/A
Case#: Female, born at term via cesarean section. Birth weight was 3.850 (+0.93-SDS); length 50 cm (+0.2-SDS); cranial circumference: 36.8 cm (+1.1-SDS).
DiseaseAssertion: MPS-IH
FamilyInfo: Proband was born to unrelated parents.
CasePresentingHPOs: Congenital hip dysplasia (detected at 2 months), systolic murmur, hepatomegaly, macrocrania, coarse facial features, umbilical hernia, corneal clouding, mild thoracic and lumbar kyphosis (HP:0001385, HP:0031664, HP:0002240, HP:0000256, HP:0000256, HP:0001537, HP:0007957, HP:0002751)
CaseHPOFreeText: Frequent episodes of upper airway inflammation, neuro-motor delay, palpable liver, mitral dysplastic valve, thickened and prolapsing flaps with moderate mitral valve insufficiency. MRI of the brain showed dilated perivascular Virchow-Robin spaces, in the peritrigonal site bilaterally and in the corpus callosum, and a slightly dilated ventricular system in the supratentorial area. Slight tibial valgus. X-rays detected an altered coxo-femoral joint with lateralization of the femoral head.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Enzymatic activity of IDUA was undetectable.
CaseUrineGAGs: An increased amount of heparan and dermatan sulfate.
CaseERT: Yes, began at 23 months. 100U/kg laronidase (Aldurazyme) weekly dose. The patient presented recurrent febrile infections and disease progression (appearance of cornea opalescence).
CaseBMT: Yes, UCB-HSCT & MUD-HSCT. First allo- HSCT from unrelated cord-blood-derived stem cells was at the age of 27 months. Six months later (33 months of age), she underwent a second HSCT from an HLA-matched unrelated donor. Normal IDUA activity was reported about 30 days post HSCT and progressively decreasing urinary GAG.
Variant1: c.152G>A (p.G51D)
Variant1ClinVarID: 193061
Variant1CAID: CA274902
Variant2: c.1598C>G (p.P533R)
Variant2ClinVarID: 11910
Variant2CAID: CA256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
distinct mutant IDUA alleles
Case#: Patient 34, Italy
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.307A>C (p.T103P)
Variant1ClinVarID: N/A
Variant1CAID: CA355960996
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
missense mutations
Case#: Patient 22, Italy
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.152G>A (p.G51D)
Variant1ClinVarID: 193061
Variant1CAID: CA274902
Variant2: c.1487C>G (p.P496R)
Variant2ClinVarID: 496861
Variant2CAID: CA2802275
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
missense mutations
Case#: Patient 12, Italy
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1044C>G (p.N348K)
Variant1ClinVarID: 557870
Variant1CAID: CA2802172
Variant2: c.1727+5G>C
Variant2ClinVarID: N/A
Variant2CAID: CA2586965991
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
distinct mutant IDUA alleles
Case#: Patient 28, Italy
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.380_382del (p.Leu127del)
Variant1ClinVarID: N/A
Variant1CAID: CA2586973517
Variant2: c.380_382del (p.Leu127del)
Variant2ClinVarID: N/A
Variant2CAID: CA2586973517
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
distinct mutant IDUA alleles
Case#: Patient 15, Italy
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.208C>T (p.Q70X)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2: c.1333_1335del (p.Asp445del)
Variant2ClinVarID: 840115
Variant2CAID: CA916082626
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
distinct mutant IDUA alleles
Case#: Patient 102, Greece
DiseaseAssertion: MPS1-H/S
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.250G>C (p.G84R)
Variant1ClinVarID: 3906899
Variant1CAID: CA355946488
Variant2: c.826G>A (p.E276K)
Variant2ClinVarID: 3233261
Variant2CAID: CA355962355
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
missense mutations
Case#: Patient 17, Italy
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.208C>T (p.Q70X)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2: c.1487C>G (p.P496R)
Variant2ClinVarID: 496861
Variant2CAID: CA2802275
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
splicing mutations
Case#: Patient 86, Turkey, patient belong to the same geographical region as patients 90, 92, and 98
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.494-1G>A
Variant1ClinVarID: 557942
Variant1CAID: CA355961634
Variant2: c.494-1G>A
Variant2ClinVarID: 557942
Variant2CAID: CA355961634
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
missense mutations
Case#: Patient 38, Poland
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.979G>C (p.A327P)
Variant1ClinVarID: 167190
Variant1CAID: CA234128
Variant2: c.1205G>A (p.W402X)
Variant2ClinVarID: 11908
Variant2CAID: CA220498
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
10
Case#: Infant #10, female.
DiseaseAssertion: MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0.70 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)
CaseUrineGAGs: DMB/Cre. Ratio - 204.70, DS - 176.96, HS - 28.51, KS - 1.78 GAG quantifications (DMB/Cre ratio) and the normal reference values based on the age groups: <6 mos: <70.68 mg /mmol cre.; 6 mos–2 yrs: <46.80 mg /mmol cre.; 2–17 yrs: <20.98 mg /mmol cre.; and >18 yrs: <12.62 mg /mmol cre. Quantitative analyses of GAG-derived disaccharides (DS, S, or KS) by tandem mass spectrometry assay. The normal cut-off values: DS < 0.80 μg/mL; HS < 0.78 μg/mL; and KS < 7.90 μg/mL.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1037T>G (p.L346R)
Variant1ClinVarID: 11927
Variant1CAID: CA256128
Variant2: c.1091C>T (p.T364M) Article has (p.364M) which appears to be a typo.
Variant2ClinVarID: 11925
Variant2CAID: CA256126
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
8
Case#: Infant #8, male.
DiseaseAssertion: MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 1.60 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)
CaseUrineGAGs: DMB/Cre. Ratio - 17.97, DS - 21.18, HS - 11.34, KS - 2.0 GAG quantifications (DMB/Cre ratio) and the normal reference values based on the age groups: <6 mos: <70.68 mg /mmol cre.; 6 mos–2 yrs: <46.80 mg /mmol cre.; 2–17 yrs: <20.98 mg /mmol cre.; and >18 yrs: <12.62 mg /mmol cre. Quantitative analyses of GAG-derived disaccharides (DS, S, or KS) by tandem mass spectrometry assay. The normal cut-off values: DS < 0.80 μg/mL; HS < 0.78 μg/mL; and KS < 7.90 μg/mL.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.300-3C>G
Variant1ClinVarID: 551563
Variant1CAID: CA549265042
Variant2: c.1874A>C (p.Y625S)
Variant2ClinVarID: 2910181
Variant2CAID: CA355965961
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
3
Case#: Infant #3, male.
DiseaseAssertion: MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 2.10 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)
CaseUrineGAGs: DMB/Cre. Ratio - 24.99, DS - 0.11, HS - 0.17, KS - 0.83 GAG quantifications (DMB/Cre ratio) and the normal reference values based on the age groups: <6 mos: <70.68 mg /mmol cre.; 6 mos–2 yrs: <46.80 mg /mmol cre.; 2–17 yrs: <20.98 mg /mmol cre.; and >18 yrs: <12.62 mg /mmol cre. Quantitative analyses of GAG-derived disaccharides (DS, S, or KS) by tandem mass spectrometry assay. The normal cut-off values: DS < 0.80 μg/mL; HS < 0.78 μg/mL; and KS < 7.90 μg/mL.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.355G>T (p.D119Y)
Variant1ClinVarID: 2432701
Variant1CAID: CA2801882
Variant2: c.617C>T (p.S206L)
Variant2ClinVarID: 1436435
Variant2CAID: CA2802033
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
27
Case#: Patient 27 (Table 3)
DiseaseAssertion: Severe naïve MPS 1
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes
CaseBMT: N/A
Variant1: c.1205G>A (p.W402X) Listed in Table 3 as c.12095G>A
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1205G>A (p.W402X) Listed in Table 3 as c.12095G>A
Variant2ClinVarID: 11908
Variant2CAID: CA220498
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
31
Case#: Patient 31 (Table 3)
DiseaseAssertion: Severe naïve MPS 1
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 2 nmol/h/mg per DBS (dried blood spots) determined during NBS. 7.57 relative protein abundance, expressed as the ratio between IDUA/GAA (amol / fmol) in buccal swabs.
CaseUrineGAGs: N/A
CaseERT: Yes
CaseBMT: N/A
Variant1: c.1898C>A (p.S633Ter)
Variant1ClinVarID: 1068474
Variant1CAID: CA355966009
Variant2: c.298A>G (p.R100G)
Variant2ClinVarID: 2058952
Variant2CAID: CA2801159
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
39
Case#: Patient 39 (Table 3)
DiseaseAssertion: Severe MPS 1
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 41 nmol/h/mg per DBS (dried blood spots) determined during NBS. 60.2 DBS protein concentration determined by Immuno-SRM (pmol/L).
CaseUrineGAGs: N/A
CaseERT: Yes
CaseBMT: N/A
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1855C>T (p.R619X)
Variant2ClinVarID: 280976
Variant2CAID: CA2802455
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Patient 2
Case#: Patient 2, Female, 5 years (report), deceased
DiseaseAssertion: Hurler Syndrome
FamilyInfo: N/A
CasePresentingHPOs: HP:0003593, HP:0001249, HP:0001510 (Infantile Onset, Mental Retardation (Severe), Growth Retardation)
CaseHPOFreeText: Organomegaly (Severe), Bone Involvement
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0 Leukocyte IDUA Activity μKat/Kg Protein
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Not Provided
Variant1: c.1650+1G>T
Variant1ClinVarID: 1323092
Variant1CAID: CA355965141
Variant2: c.1650+1G>T
Variant2ClinVarID: 1323092
Variant2CAID: CA355965141
AdditionalVariants: N/A
ParentalGenotype: Both parents had the c.1650 + 1G > T variant on Allele 1, but were normal on Allele 2
PreviouslyPublished: N/A
Patient 3
Case#: Patient 3, Male, 3 years (report), deceased
DiseaseAssertion: Hurler Syndrome
FamilyInfo: N/A
CasePresentingHPOs: HP:0003593, HP:0001249 (Infantile Onset, Mental Retardation (Severe))
CaseHPOFreeText: Organomegaly (Severe), Bone Involvement
CaseNotHPOs: HP:0001510 (Growth Retaradtion)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0.044 Leukocyte IDUA Activity μKat/Kg Protein
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Not Provided
Variant1: c.1650+1G>T
Variant1ClinVarID: 1323092
Variant1CAID: CA355965141
Variant2: p.A75T
Variant2ClinVarID: 222993
Variant2CAID: CA356994
AdditionalVariants: N/A
ParentalGenotype: The mother carries the c.1650 + 1G > T variant on Allele 1, and the father carries the p.A75T variant on Allele 1, but both were normal on Allele 2
PreviouslyPublished: N/A
Patient 4
Case#: Patient 4, Male, 2 years (report),
DiseaseAssertion: Hurler Syndrome
FamilyInfo: N/A
CasePresentingHPOs: HP:0003593 (Infantile Onset)
CaseHPOFreeText: Organomegaly (Severe), Bone Involvement
CaseNotHPOs: HP:0001249, HP:0001510 (Mental Retardation, Growth Retardation)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0 Leukocyte IDUA Activity μKat/Kg Protein
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Not Provided
Variant1: c.1650+1G>T
Variant1ClinVarID: 1323092
Variant1CAID: CA355965141
Variant2: p.R555H
Variant2ClinVarID: 2151983
Variant2CAID: CA2802347
AdditionalVariants: N/A
ParentalGenotype: The mother carried the c.1650 + 1G > T variant on Allele 1 and the father carried the p.R555H variant on allele 1, but both were normal on Allele 2
PreviouslyPublished: N/A
older sibling
Case#: OS of sibship 4, male, 3.6 years old (age at diagnosis), 5.5 years old (age at ERT enrollment), 3.5 years (duration of ERT)
DiseaseAssertion: MPS1-HS
FamilyInfo: Affected male YS (YS of sibship 4)
CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828, HP:0001263 (Corneal opacity, dysostosis, joint contractures, cognitive delays)
CaseHPOFreeText: Cardiac disease (developed after T1), progression of respiratory symptoms
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes - Had poor compliance (~60 %) with ERT, which may have impacted the symptom progression.
CaseBMT: N/A
Variant1: c.623G>A (p.G208D)
Variant1ClinVarID: 554590
Variant1CAID: CA355961948
Variant2: (p.P520R), Typo, no proline at this position
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
younger sibling
Case#: YS of sibship 3, female, 0.4 years old (age at diagnosis), 0.7 years old (age at ERT enrollment), 8.3 years (duration of ERT)
DiseaseAssertion: MPS1-HS
FamilyInfo: Affected female OS (OS of sibship 3)
CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contractures)
CaseHPOFreeText: Cardiac disease, mild musculoskeletal symptoms, mild to moderate ocular disease.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes - After 8 years of ERT had no restrictions in ADL, no cognitive delays, and only mild musculoskeletal symptoms and mild to moderate ocular disease and cardiac symptoms remained stable.
CaseBMT: N/A
Variant1: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Biochemical Characteristics of iPSC-Derived Dopaminergic Neurons from N370S GBA Variant Carriers with and without Parkinson’s Disease
PMID: 36901867
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
26
Case#: Patient 26, born in 2010 (paper published in 2017), 7 months (age at first treatment)
DiseaseAssertion: MPSI-H
FamilyInfo: N/A
CasePresentingHPOs: Corneal clouding (HP:0007957)
CaseHPOFreeText: N/A
CaseNotHPOs: Cataract, retinopathy (HP:0000518, HP:0000488)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 71 ng/mol (43 weight matched enzyme reference assay)
CaseUrineGAGs: 0.42 DS/CS
CaseERT: Yes
CaseBMT: Yes, Cord
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1205G>A (p.W402X)
Variant2ClinVarID: 11908
Variant2CAID: CA220498
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
12
Case#: Patient 12, born in 2006 (paper published in 2017), 13 months (age at first treatment)
DiseaseAssertion: MPSI-H
FamilyInfo: N/A
CasePresentingHPOs: Corneal clouding (HP:0007957)
CaseHPOFreeText: N/A
CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 41.12 ng/mol (17.84 weight matched enzyme reference assay)
CaseUrineGAGs: 0.37 DS/CS
CaseERT: Yes
CaseBMT: Yes, Cord
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1205G>A (p.W402X)
Variant2ClinVarID: 11908
Variant2CAID: CA220498
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
23
Case#: Patient 23, born in 1992 (paper published in 2017), 15 months (age at first treatment), 18 months (age at last treatment)
DiseaseAssertion: MPSI-H
FamilyInfo: N/A
CasePresentingHPOs: Corneal clouding, retinopathy (HP:0007957, HP:0000488)
CaseHPOFreeText: N/A
CaseNotHPOs: Cataract (HP:0000518)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 36.55 ng/mol (67.98 weight matched enzyme reference assay)
CaseUrineGAGs: 0.60 DS/CS
CaseERT: No
CaseBMT: Yes, MUD
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1598C>G (p.P533R)
Variant2ClinVarID: 11910
Variant2CAID: CA256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
16
Case#: Patient 16, born in 2004 (paper published in 2017), 15 months (age at first treatment)
DiseaseAssertion: MPSI-H
FamilyInfo: N/A
CasePresentingHPOs: Corneal clouding (HP:0007957)
CaseHPOFreeText: N/A
CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 52.1 ng/mol (26 weight matched enzyme reference assay)
CaseUrineGAGs: 0.22 DS/CS
CaseERT: Yes
CaseBMT: Yes, Cord
Variant1: c.386-2A>G
Variant1ClinVarID: 222994
Variant1CAID: CA356991
Variant2: c.41T>G (p.L14R)
Variant2ClinVarID: N/A
Variant2CAID: CA355945322
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
7/f
Case#: Patient 7, female, 8.2 months (age at diagnosis), 11.4 months (age at HSCT), 9.7 - 14.0 months (age at ERT), 4 MRI + neuropsychological observations over the course of 9 years.
DiseaseAssertion: MPS-1H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 68.0 nmol/h/mg (Normal values: 11-43 nmol/h/mg)
CaseUrineGAGs: N/A
CaseERT: Yes
CaseBMT: Yes, transplanted with an unrelated cord blood unit.
Variant1: c.1205G>A (p.W402)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1205G>A (p.W402X)
Variant2ClinVarID: 11908
Variant2CAID: CA220498
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
2/f
Case#: Patient 2, female, 13.7 months (age at diagnosis), 22.2 months (age at HSCT) - failed & 43.2 months (age at 2nd HSCT), 7 MRI + neuropsychological observations over the course of 16 years.
DiseaseAssertion: MPS-1H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 43 nmol/h/mg (Normal values: 11-43 nmol/h/mg)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: Yes, failed
Variant1: c.1163delC (p.T388fs)
Variant1ClinVarID: 828094
Variant1CAID: CA915942984
Variant2: c.152G>A (p.G51D)
Variant2ClinVarID: 193061
Variant2CAID: CA274902
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Hurler disease
Case#: Patient 7, 8 months old (age at report), male, Indian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, recurrent infections, dysostosis multiplex, intellectual disability (HP:0000280, HP:0001433, HP:0007957, HP:0002719, HP:0000943, HP:0001249)
CaseHPOFreeText: Cardiac disease
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 2.8% (Range of residual enzyme activity: 0.0%-4.8%)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.367G>A (p.Glu123Lys)
Variant1ClinVarID: 196235
Variant1CAID: CA243126
Variant2: c.367G>A (p.Glu123Lys)
Variant2ClinVarID: 196235
Variant2CAID: CA243126
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Hurler disease
Case#: Patient 60, 14 years old (age at report), male, Indian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, dysostosis multiplex, intellectual disability, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0000943, HP:0001249, HP:0100790)
CaseHPOFreeText: Cardiac disease
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1181_1189dup (p.Ala394_Leu396dup)
Variant1ClinVarID: 3720561
Variant1CAID: CA549264540
Variant2: c.1898C>T (p.Ser633Leu)
Variant2ClinVarID: 556406
Variant2CAID: CA355966010
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Hurler disease
Case#: Patient 18, 3 months old (age at report), male, Indian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Coarse facial features (HP:0000280)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 3.9% (Range of residual enzyme activity: 0.0%-4.8%)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.784delC (p.His262Thrfs*55)
Variant1ClinVarID: 956890
Variant1CAID: CA2802083
Variant2: c.784delC (p.His262Thrfs*55)
Variant2ClinVarID: 956890
Variant2CAID: CA2802083
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Hurler disease
Case#: Patient 41, 4 years old (age at report), female, Indian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, recurrent infections, dysostosis multiplex (HP:0000280, HP:0001433, HP:0007957, HP:0002719, HP:0000943)
CaseHPOFreeText: Cardiac disease
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1855C>T (p.Arg619Ter)
Variant1ClinVarID: 280976
Variant1CAID: CA2802455
Variant2: c.1855C>T (p.Arg619Ter)
Variant2ClinVarID: 280976
Variant2CAID: CA2802455
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Hurler disease
Case#: Patient 33, 5 years old (age at report), male, Indian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0100790)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 1.8% (Range of residual enzyme activity: 0.0%-4.8%)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1373T>C (p.Leu458Pro)
Variant1ClinVarID: N/A
Variant1CAID: CA355964255
Variant2: c.1373T>C (p.Leu458Pro)
Variant2ClinVarID: N/A
Variant2CAID: CA355964255
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Lysosomal storage disorders: Novel and frequent pathogenic variants in a large cohort of Indian patients of Pompe, Fabry, Gaucher and Hurler disease
PMID: 33301762
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Hurler disease
Case#: Patient 40, 1 years old (age at report), male, Indian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Coarse facial features, hepatosplenomegaly (HP:0000280, HP:0001433)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1750C>T (p.Gln584Ter)
Variant1ClinVarID: 846228
Variant1CAID: CA355965360
Variant2: c.1750C>T (p.Gln584Ter)
Variant2ClinVarID: 846228
Variant2CAID: CA355965360
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Hurler disease
Case#: Patient 56, 4 years old (age at report), female, Indian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Coarse facial features, joint contractures (HP:0000280, HP:0002828)
CaseHPOFreeText: Cardiac disease
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.589G>A (p.Gly197Ser)
Variant1ClinVarID: 1526094
Variant1CAID: CA355961839
Variant2: c.1026G>A (p.Trp402Ter) in the article but this is not a valid variant. Could possible be c.1205G>A (p.Trp402Ter)
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
P5-IDUAFWest AfricaNigeria1.393.48IDUAc.235G > A/+p.Ala79Thr/+MissensePseudo
Case#: P5-IDUA, F, West Africa, Nigeria DiseaseAssertion: MPS1 - Pseudo/VUS FamilyInfo: CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: NBS 1.4 triplex / 3.8 single CaseUrineGAGs: CaseERT: CaseBMT: Variant1: c.246C>G Variant1ClinVarID: 92637 Variant1CAID: CA220506 Variant2: c.1716C>G Variant2ClinVarID: 1431214 Variant2CAID: CA355965272 AdditionalVariants: ParentalGenotype: PreviouslyPublished
three cases
Case#: 2 (16 y, male - brother of Case 1, symptom onset/pain+movement limitation 8 y, diagnosis 16y)
DiseaseAssertion: Scheie syndrome
FamilyInfo: Male patient born to consanguineous parents
CasePresentingHPOs: 0034337
CaseHPOFreeText: claw hands with flexion contractures; electroneurology showed bilateral signs of mild median nerve suffering.
CaseNotHPOs: HP:0000280; HP:0001510; HP:0000943
CaseNotHPOFreeText: no coarse face, growth failure, other joint involvement, evidence of dysostosis multiplex of other bones. Normal intelligence, ophthalmologic, hearing and echocardiography, brain MRI
CaseEnzymeAssay: 0.64 (umol/g/h)
CaseUrineGAGs:
CaseERT: Yes, after diagnosis at 16y CaseBMT:
Variant1:c.1189+4A>T
Variant1ClinVarID:
Variant1CAID: CA2586965965
Variant2: 1189+4A>T
Variant2ClinVarID:
Variant2CAID: CA2586965965
AdditionalVariants:
ParentalGenotype:
PreviouslyPublished
3
Case#: Patient No. 3 (Table 1), White race, female, 1.95 years old (age at time of gene therapy), 75 IQ score, 2.13 years since gene therapy (2 years since latest visit).
DiseaseAssertion: MPS-IH
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: Yes
Variant1: c.208C>T (p.Q70X)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2: c.208C>T (p.Q70X)
Variant2ClinVarID: 11909
Variant2CAID: CA204563
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Identification of an α-l-iduronidase (IDUA) M1T mutation in a Chinese family with autosomal recessive mucopolysaccharidosis I
PMID: 37347427
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Case#: CA-118 ID number, Table S1.1 of Supplementary Material. Male, at birth (age at first symptoms), 1 year and 3 months old (age at diagnosis). Failed newborn hearing test, behind on milestones such as walking, sitting, and crawling. Goes to PT weekly. Stored frozen (-20ºC) 2.8 yr
DiseaseAssertion: Severe MPS-I
FamilyInfo: N/A
CasePresentingHPOs: Delayed speech, kyphosis, enlarged tonsils, corneal clouding, constipation, hearing impairment, central sleep apnea, obstructive sleep apnea, (HP:0000750, HP:0002808, HP:0030812, HP:0007957, HP:0002019, HP:0000365, HP:0010536, HP:0002870)
CaseHPOFreeText: Leaky mitral valve, physical delays.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: 933 fmol/punch
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1598C>G (p.P533R)
Variant2ClinVarID: 11910
Variant2CAID: CA256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Case#: NJ-501 ID number, Table S1.1 of Supplementary Material. Male, 1 year and 1 month (age at first symptoms), 1 year and 2 months old (age at diagnosis). Stored ambient 3 yr
DiseaseAssertion: Severe MPS-I
FamilyInfo: N/A
CasePresentingHPOs: Macrocephaly, kyphosis, coarse facial features, corneal clouding, hearing impairment, developmental delays, speech delays (HP:0000256, HP:0002808, HP:0000280, HP:0007957, HP:0000365, HP:0001263, HP:0000750)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: 1147 fmol/punch
CaseERT: N/A
CaseBMT: N/A
Variant1: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Case#: CA-129 ID number, Table S1.1 of Supplementary Material. Female, 5 months old (age at first symptoms), 8 months old (age at diagnosis). Stored frozen (-20ºC) 14.8 yr.
DiseaseAssertion: Severe MPS-I
FamilyInfo: N/A
CasePresentingHPOs: Congestion, macrocephaly, pain, musculoskeletal deformities, short stature, short neck, corneal clouding (HP:0001742, HP:0000256, HP:0012531, HP:0011843, HP:0004322, HP:0000470, HP:0007957)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: 1083 fmol/punch
CaseERT: N/A
CaseBMT: N/A
Variant1: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Case#: NY-607 ID number, Table S1.1 of Supplementary Material. Additional health information not provided.
DiseaseAssertion: Severe MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: 2169 fmol/punch
CaseERT: N/A
CaseBMT: N/A
Variant1: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Case#: TW1-2 ID number, Table S1.1 of Supplementary Material. Female, 1-2 years old (age at first symptoms), 3 years and 2 months old (age at diagnosis). Stored Frozen (-20ºC).
DiseaseAssertion: Severe MPS-I
FamilyInfo: Twin of patient TW1-3.
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: 615 fmol/punch
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1037T>G (p.L346R)
Variant1ClinVarID: 11927
Variant1CAID: CA256128
Variant2: c.1091C>T (p.T364M)
Variant2ClinVarID: 11925
Variant2CAID: CA256126
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
infant B
Case#: Infant B
DiseaseAssertion: MPSI
FamilyInfo:
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: Newborn screening, dried blood spot, modification of method published by Chamoles et al, IDUA activity <9.03 umol/L blood*20 on initial and repeat testing.
CaseUrineGAGs: Urinary GAG obtained as part of confirmatory testing but results are not presented.
CaseERT:
CaseBMT:
Variant1: c.344 G>T (D119Y), paternal origin
Variant1ClinVarID:
Variant1CAID:
Variant2: c.99 T>G (H33Q), maternal origin
Variant2ClinVarID:
Variant2CAID:
AdditionalVariants:
ParentalGenotype: c.344 G>T (paternal) / c.99 T>G (maternal)
PreviouslyPublished No
infant A
Case#: Infant A
DiseaseAssertion: MPSI
FamilyInfo:
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: Newborn screening, dried blood spot, modification of method published by Chamoles et al, IDUA activity <9.03 umol/L blood*20 on initial and repeat testing.
CaseUrineGAGs: Urinary GAG obtained as part of confirmatory testing but results are not presented.
CaseERT: Don't know
CaseBMT: Don't know
Variant1: 303G > A (R105Q), paternal origin
Variant1ClinVarID: 2020010
Variant1CAID: CA2801866
Variant2: c.484 G>A (R162K), maternal origin
Variant2ClinVarID: 550594
Variant2CAID: CA355961605
AdditionalVariants:
ParentalGenotype: c.303 G>A (paternal) / c.484 G>A (maternal)
PreviouslyPublishedNo
10
Case#: Patient 10, male, 2 years (age at presentation).
DiseaseAssertion: MPS1-H
FamilyInfo: Consanguinity in the family present for this patient.
CasePresentingHPOs: Corneal clouding, coarse facial features, cardiomegaly, dystosis multiplex, global developmental delay, hepatomegaly, joint stiffness, recurrent respiratory infections, sleep disturbances (HP:0007957, HP:0000256, HP:0001640, HP:0000943, HP:0001263, HP:0002240, HP:0001387, HP:0002205, HP:0002360)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.540G>A (p.W180X)
Variant1ClinVarID: 1321357
Variant1CAID: CA355961724
Variant2: c.540G>A (p.W180X)
Variant2ClinVarID: 1321357
Variant2CAID: CA355961724
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
21
Case#: Patient 21, male, 4 years (age at presentation).
DiseaseAssertion: MPS1-H/S
FamilyInfo: Consanguinity in the family present for this patient.
CasePresentingHPOs: Corneal clouding, coarse facial features, dystosis multiplex, hepatomegaly, joint stiffness, motor delay, splenomegaly (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0001387, HP:0001270, HP:0001744)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1469T>C (p.L490P)
Variant1ClinVarID: 11919
Variant1CAID: CA220503
Variant2: c.1469T>C (p.L490P)
Variant2ClinVarID: 11919
Variant2CAID: CA220503
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
10/F
Case#: 10, Female, Han Chinese
DiseaseAssertion: Hurler-Scheie Syndrome
FamilyInfo: Not Provided
CasePresentingHPOs: HP:0001433, HP:0001387, HP:0007957 (Hepatosplenomegaly, Joint Stiffness, Corneal Clouding)
CaseHPOFreeText: Slight Mental Delay
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0.18 Leukocyte IDUA activity (nmol/h/mg protein) (isolated leukocytes in the latter)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Using the artificial substrate 4-methyl-umbelliferyl α-L-iduronide (Sigma)
Variant1: c.1190-1G>A
Variant1ClinVarID: 1204494
Variant1CAID: CA355963511
Variant2: p.R363H
Variant2ClinVarID: N/A
Variant2CAID: CA355963308
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
p.Q310X
This variant is mentioned in the text as not having been found in the Han Chinese.
3/m
Case#: 3, Male, Han Chinese
DiseaseAssertion: Hurler Syndrome
FamilyInfo: Not Provided
CasePresentingHPOs: HP:0001249, HP:0007957, HP:0001433 (Mental Retardation (severe), Corneal Clouding, Hepatosplenomegaly)
CaseHPOFreeText: Skeletal Deformities
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0 Leukocyte IDUA activity (nmol/h/mg protein) (isolated leukocytes in the latter)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Using the artificial substrate 4-methyl-umbelliferyl α-L-iduronide (Sigma)
Variant1: c.1190-1G>A
Variant1ClinVarID: 1204494
Variant1CAID: CA355963511
Variant2: c.792+1G>T
Variant2ClinVarID: N/A
Variant2CAID: CA355962278
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
3
Case#: Subject 3, female, in her 20s (age at enrollment)
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: HP:0002176 (Spinal cord compression)
CaseHPOFreeText: Disappearance of Hoffmann's reflex
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes - Enzyme replacement therapy with laronidase, did not enroll in extension study
CaseBMT: N/A
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1577T>C (p.L526P)
Variant2ClinVarID: 567566
Variant2CAID: CA2802300
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Safety of laronidase delivered into the spinal canal for treatment of cervical stenosis in mucopolysaccharidosis I
PMID: 26260077
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
2
Case#: Subject 2, female, in her 10s (age at enrollment)
DiseaseAssertion: MPS1-HS
FamilyInfo: N/A
CasePresentingHPOs: HP:0000012, HP:0000020, HP:0007340, HP:0002176 (Urinary urgency, urinary incontinence, lower limb muscle weakness, spinal cord compression)
CaseHPOFreeText: Anti-iduronidase antibodies, leukocytes
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes - Off-study, off-label with intrathecal laronidase beginning ~16 months prior to enrollment in the extension study, received prophylaxis with oral prednisone prior to intrathecal laronidase.
CaseBMT: N/A
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.713T>A (p.L238Q)
Variant2ClinVarID: 265418
Variant2CAID: CA2802065
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Identification of infants at risk for developing Fabry, Pompe or Mucopolysaccharidosis-I from newborn blood spots by tandem mass spectrometry
PMID:23465405
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Variant 5 of 11
Variant1:NM_000203.3: c.1641dup p.(Pro548Alafs*24)
Variant1CAID:CA2586965989
Variant 4 of 11
Variant1:NM_000203.3: c.1599del p.(Ser534Argfs*26)
Variant1CAID:CA2586965987
3
Case#: 3, Male, 0.2 years (diagnosed), 1.5 years (report), 7.5 kg (weight), 72 cm (height), Iranian
DiseaseAssertion: Hurler-Scheie Syndrome
FamilyInfo: Parents are consanguineous
CasePresentingHPOs: N/A
CaseHPOFreeText: Chronic Rhinorrhea
CaseNotHPOs: HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0100790, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia, Deafness, Corneal Opacity, Hydrocephalus)
CaseNotHPOFreeText: HM/HSM, Cardiac Manifestations
CaseEnzymeAssay: IDUA activity 0.76 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 10.80 (mg/gCr)
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sanger Sequencing
Variant1: p.Y109H
Variant2: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
15
Case#: 15, Male, 0.7 years (diagnosed), 4.2 years (report), 10.1 kg (weight), 60 cm (height), Iranian
DiseaseAssertion: Hurler-Scheie Syndrome
FamilyInfo: Parents are not consanguineous
CasePresentingHPOs: HP:0001249, HP:0001999, HP:0100790 (Mental Retardation, Facial Dysmorphic Features, Hernia)
CaseHPOFreeText: HM/HSM
CaseNotHPOs: HP:0000943, HP:0001387, HP:0000365, HP:0007957, HP:0000238 (Multiple Dysostosis, Joint Stiffness, Deafness, Corneal Opacity, Hydrocephalus)
CaseNotHPOFreeText: Chronic Rhinorrhea, Cardiac Manifestations
CaseEnzymeAssay: IDUA activity 0.23 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 7.42 (mg/gCr)
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sanger Sequencing
Variant1: p.G84R
Variant2: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
20
Case#: 20, Female, 1.3 years (diagnosed), 12.5 years (report), 23 kg (weight), 80 cm (height), Iranian
DiseaseAssertion: Scheie Syndrome
FamilyInfo: Parents are not consanguineous
CasePresentingHPOs: HP:0001999, HP:0100790 (Facial Dysmorphic Features, Hernia)
CaseHPOFreeText: N/A
CaseNotHPOs: HP:0001249, HP:0000943, HP:0001387, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Multiple Dysostosis, Joint Stiffness, Deafness, Corneal Opacity, Hydrocephalus)
CaseNotHPOFreeText: HM/HSM, Chronic Rhinorrhea, Cardiac Manifestations
CaseEnzymeAssay: IDUA activity 2.3 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 7.6 (mg/gCr)
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sanger Sequencing
Variant1: Not Provided
Variant2: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Abnormal
Case#:No additional case information provided.
DiseaseAssertion: Not specified
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Abnormal
CaseUrineGAGs: Normal
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1577T>C (p.p.L526P)
Variant1ClinVarID: 567566
Variant1CAID: CA2802300
Variant2: c.536C>T (p.T179M)
Variant2ClinVarID: 1455223
Variant2CAID: CA2801986
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Abnormal
Case#: No additional case information provided
DiseaseAssertion: MPS-IH
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Abnormal
CaseUrineGAGs: Abnormal
CaseERT: N/A
CaseBMT: N/A
Variant1: c.568_581del14 (p.N190HfsTer?)
Variant1ClinVarID: 3639714
Variant1CAID: CA2801994
Variant2: c.568_581del14 (p.N190HfsTer?)
Variant2ClinVarID: 3639714
Variant2CAID: CA2801994
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Abnormal
Case#: No additional case information provided.
DiseaseAssertion: Not specified
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Abnormal
CaseUrineGAGs: Normal
CaseERT: N/A
CaseBMT: N/A
Variant1: c.250G>A (p.p.G48S)
Variant1ClinVarID: 726495
Variant1CAID: CA2801152
Variant2: c.793-9C>A
Variant2ClinVarID: 2193713
Variant2CAID: CA2802095
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Abnormal
Case#: No additional case information provided
DiseaseAssertion: MPSI-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Abnormal
CaseUrineGAGs: Abnormal
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1402+1G>T
Variant2ClinVarID: 1323099
Variant2CAID: CA355964387
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
case 1
Case#: Case 1, male, 2 years old (age at diagnosis).
DiseaseAssertion: MPS1
FamilyInfo: Proband's mother was pregnant and her genomic DNA was extracted from cultured amniocytes, her fetus did not acquire the same pathogenic gene as the proband and was a normal fetus.
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Proband was diagnosed using enzymatic detection. IDUA enzyme activity in the mother's amniotic fluid cells in the 2nd pregnancy was 9.0 nmol/(h·mg protein).
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.713T>G (p.Leu238Arg)
Variant1ClinVarID: 2581619
Variant1CAID: CA2802064
Variant2: c.882dupC, in the article this is written as c.883insC (old nomenclature). Various variants from Wang articles have nomenclature errors that are 1 base pair off from the described variant.
Variant2ClinVarID: 1076379
Variant2CAID: CA2499217013
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: A591T
Variant1ClinVarID: 92635
Variant1CAID: CA145876
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: R162I
Variant1ClinVarID:
Variant1CAID: CA355961607
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: R89Q
Variant1ClinVarID: 11922
Variant1CAID: CA256124
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: G84R
Variant1ClinVarID:
Variant1CAID: CA355946488
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: M504T
Variant1ClinVarID:
Variant1CAID: CA355964770
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: G197D
Variant1ClinVarID: 554670
Variant1CAID: CA91167598
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: P496L
Variant1ClinVarID: 551675
Variant1CAID: CA91170412
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: G265R
Variant1ClinVarID: 638074
Variant1CAID: CA2802098
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: R489P
Variant1ClinVarID: 1518214
Variant1CAID: CA355964650
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: R105Q
Variant1ClinVarID: 92641
Variant1CAID: CA145881
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: D349Y
Variant1ClinVarID: 638075
Variant1CAID: CA355963146
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: A160D
Variant1ClinVarID:
Variant1CAID: CA355961593
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: A327P
Variant1ClinVarID: 167190
Variant1CAID: CA234128
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4
DiseaseAssertion: Mucopolysaccharidosis type I, MPS I
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: A319V
Variant1ClinVarID: 1683230
Variant1CAID: CA2802126
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
710.495 (5.9)10.8DS 3.6homozygous PD: c.235G>A; p.A79TNormal examinationHS 3.3heterozygous PD: c.296C>T; p.T99Iheterozygous PD: c.1225G>C; p.G409R
Case#:Patient Sample unique ID 71, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)
DiseaseAssertion:None
FamilyInfo:None
CasePresentingHPOs:None
CaseHPOFreeText:None
CaseNotHPOs:None
CaseNotHPOFreeText: Normal examination at follow up after screening positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)
CaseEnzymeAssay: IDUA activity 0.495 (5.9) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 10.8 pmol/punch/h Confirmatory IDUA enzyme
CaseUrineGAGs: DS 3.6 g/mol creatinine and HS 3.3 g/mol creatinine (Normal)
CaseERT:No
CaseBMT:No
Variant1:homozygous PD: c.235G>A; p.A79T (Normal examination)
Variant1ClinVarID:41682
Variant1CAID: CA000358
Variant2: homozygous PD: c.296C>T; p.T99I
Variant2ClinVarID:53610
Variant2CAID:CA326991
AdditionalVariants:heterozygous PD: c.1225G>C; p.G409R (ClinVarID: 92627, CAID: CA248659)
ParentalGenotype:None provided
PreviouslyPublished:N/A
40.280 (4.2)2DS 5.7heterozygous VUS: c.1582C>G; p.P528ANormal examinationHS 3.6heterozygous likely benign: c.240C>Ghomozygous PD: c.235G>A; p.A79Thomozygous PD: c.296C>T; p.T99I
Case#:Patient Sample unique ID 4, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)
DiseaseAssertion:None at follow up after screening positive at birth
FamilyInfo:None
CasePresentingHPOs:None
CaseHPOFreeText: None
CaseNotHPOs:None
CaseNotHPOFreeText: Normal examination at follow up after screening positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)
CaseEnzymeAssay: IDUA activity 0.280 (4.2) umol/L/h (%DMA) through dried blood spot during newborn screening and 2 pmol/punch/h Confirmatory IDUA enzyme measured at follow-up appointment
CaseUrineGAGs: DS 5.7 g/mol creatinine and HS 3.6 g/mol creatinine (Normal)
CaseERT:No
CaseBMT:No
Variant1:heterozygous VUS: c.1582C>G; p.P528A
Variant1ClinVarID:2880182
Variant1CAID:CA398172227
Variant2: heterozygous likely benign: c.240C>G
Variant2ClinVarID: 4549
Variant2CAID: CA253209
AdditionalVariants:homozygous PD: c.235G>A; p.A79T (ClinVarID:41682, CA000358) and homozygous PD: c.296C>T; p.T99I (ClinVarID:53610, CA326991)
ParentalGenotype:N/A
PreviouslyPublished:N/A
rare polymorphism (A591T)
Case#: Family 16, Italy
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.
α-L-iduronidase activity in COS-7 cells transiently transfected with wild-type or mutagenised cDNAs. α-L-iduronidase activity: 4.9 nmol/h/mg cell protein (p.P496R), 99.3 nmol/h/mg cell protein (p.A591T); values are the means of two experiments.
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.878_889dup (p.Thr293_Tyr296dup); c.974ins12 in the paper (old nomenclature
Variant1ClinVarID: 550382
Variant1CAID: CA2802114
Variant2: c.1487C>G (p.P496R)
Variant2ClinVarID: 496861
Variant2CAID: CA2802275
AdditionalVariants: 1771G>A (p.A591T) The polymorphism and novel missense mutations were transiently expressed in COS-7 cells and all of them except the polymorphism showed complete loss of enzyme activity.
ParentalGenotype: N/A
PreviouslyPublished N/A
R628X
Case#: Family 3, Middle East
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1882C>T (p.R628X)
Variant1ClinVarID: 550421
Variant1CAID: CA2802462
Variant2: c.1882C>T (p.R628X)
Variant2ClinVarID: 550421
Variant2CAID: CA2802462
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Y167X
Case#: Family 28, India
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: The Scheie phenotype is characterized by aortic valve disease, corneal clouding, limited skeletal problems, but no mental retardation. This is a general assessment and not specific to this patient.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.
α-L-iduronidase activity in COS-7 cells transiently transfected with wild-type or mutagenised cDNAs. α-L-iduronidase activity: 4.5 nmol/h/mg cell protein; values are the means of two experiments.
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.501C>G (p.Y167X)
Variant1ClinVarID: 92644
Variant1CAID: CA220511
Variant2: c.614G>A (p.C205Y)
Variant2ClinVarID: 1468875
Variant2CAID: CA355961928
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
PMID: 8213840
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Scheie
Case#: 1.8% residual activity at 37 °C
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 4.9 ± 1.5 nmol/mg/h IDUA activity at 37 °C
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.826G>A (p.E276K)
Variant1ClinVarID: 3233261
Variant1CAID: CA355962355
Variant2: c.826G>A (p.E276K)
ClinVarID: 3233261
Variant2CAID: CA355962355
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Hurler/Scheie
Case#: 0.3% residual activity at 37 °C
DiseaseAssertion: MPS1-H/S
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0.8 ± 0.3 nmol/mg/h IDUA activity at 37 °C
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1598C>G (p.P533R)
Variant1ClinVarID: 11910
Variant1CAID: CA256112
Variant2: c.1598C>G (p.P533R)
ClinVarID: 11910
Variant2CAID: CA256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Scheie
Case#: 0.6% residual activity at 37 °C
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 1.6 ± 0.1 nmol/mg/h IDUA activity at 37 °C
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.979G>C (p.A327P)
Variant1ClinVarID: 167190
Variant1CAID: CA234128
Variant2: N/A
ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Scheie
Case#: 1.2% residual activity at 37 °C
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 3.3 ± 1.1 nmol/mg/h IDUA activity at 37 °C
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.826G>A (p.E276K)
Variant1ClinVarID: 3233261
Variant1CAID: CA355962355
Variant2: c.826G>A (p.E276K)
ClinVarID: 3233261
Variant2CAID: CA355962355
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Scheie
Case#: 0.9% residual activity at 37 °C
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 2.5 ± 0.2 nmol/mg/h IDUA activity at 37 °C
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1861C>T (p.R621X)
Variant1ClinVarID: 11917
Variant1CAID: CA256118
Variant2: c.974ins12 in paper but nomenclature is c.878_889dup (p.Thr293_Tyr296dup)
ClinVarID: 550382
Variant2CAID: CA2802114
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Analysis of cDNA molecules is not suitable for the molecular diagnosis of Mucopolysaccharidosis type I
PMID: 22306676
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
4/F
Case#: Patient 4, female, Russian
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: Moderate mental delay, hepatosplenomegaly, joint stiffness, corneal clouding (HP:0002342, HP:0001433, HP:0001387, HP:0007957)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 7.7 nmol/mg/h (reference range 135 ± 57 nmol/mg/h)
CaseUrineGAGs: 20.79 mg GAG/mmol/creatinine (reference range 6.17 ± 3.79 mg GAG/mmol creatinine)
CaseERT: No
CaseBMT: No
Variant1: c.314G>A (p.R105Q)
Variant1ClinVarID: 92641
Variant1CAID: CA145881
Variant2: c.1081G>A (p.A361T)
Variant2ClinVarID: 92624
Variant2CAID: CA145865
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
2/M
Case#: Patient 2, male, Russian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Severe intellectual disability, corneal clouding, skeletal deformities, hepatosplenomegaly (HP:0010864, HP:0007957, HP:0000924, HP:0001433)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0.4 nmol/mg/h (reference range 135 ± 57 nmol/mg/h)
CaseUrineGAGs: 42.19 mg GAG/mmol/creatinine (reference range 6.17 ± 3.79 mg GAG/mmol creatinine)
CaseERT: No
CaseBMT: No
Variant1: c.1044C>G (p.N348K)
Variant1ClinVarID: 557870
Variant1CAID: CA2802172
Variant2: c.718C>G (p.H240D)
Variant2ClinVarID: 2654540
Variant2CAID: CA355962125
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Patients of family A
Case#: Family A proband, male, 11 years old (diagnosis), Tunisia.
DiseaseAssertion: MPS1-S
FamilyInfo: No other affected family members (See Fig. 1). Parents are 3rd degree relatives (See Table 1).
CasePresentingHPOs: HP:0001263, HP:0000280, HP:0000238, HP:0001433, HP:0000158, HP:0012471, HP:0000574, HP:0000520, HP:0000365, HP:0004322 (Global developmental delay, course facial features, hydrocephalus, hepatosplenomegaly, macroglossia, thick lips, bushy eyebrows, exophthalmos, hearing loss, short stature)
CaseHPOFreeText: Noisy breathing
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA activity (0.1 nmol/h/mg) (usual values: 1-5)
CaseUrineGAGs: glycosaminoglycans (136 mg/g of creatinine) (usual values: 6-23), abnormal electrophoresis profile (dermatan sulfate and heparan sulfate).
CaseERT: No
CaseBMT: No
Variant1: c.1598C>G (p.P533R)
Variant1ClinVarID:11910
Variant1CAID: CA256112
Variant2: c.1598C>G (p.P533R)
Variant2ClinVarID: 11910
Variant2CAID: CA256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Patient of family C
Case#: Family C proband, male, 1 year and 8 months old (age of diagnosis), 2 years old (age of death), Tunisia.
DiseaseAssertion: MPS1-H
FamilyInfo: No affected family members (See Fig. 1). Parents were 1st degree relatives (First child of first cousins) (See Table 1).
CasePresentingHPOs: HP:0001263, HP:0000280, HP:0001131, HP:0001513 (Global developmental delay, course facial features, corneal dystrophy, obesity)
CaseHPOFreeText: Abnormal flexibility of joints
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: DUA activity (0.1 nmol/h/mg) (usual values: 1-5)
CaseUrineGAGs: Glycosaminoglycans (116 mg/g of creatinine) (usual values: 9-46), abnormal electrophoresis profile with dermatan sulfate and heparan sulfate.
CaseERT: No
CaseBMT: No
Variant1: c.1587_1588dup (p.Leu530Argfs*31) (Information pulled from separate article PMID: 21639919) Article had written p.L530fs (1587_1588 insGC) (See article 12). However, upon looking at the chromatogram (Fig. 2), it was noted that there was an error in the nomenclature. A duplication had occurred rather than an insertion.
Variant1ClinVarID: 2203498
Variant1CAID: CA2580616050
Variant2: c.1587_1588dup (p.Leu530Argfs*31) (Information pulled from separate article PMID: 21639919)
Variant2ClinVarID: 2203498
Variant2CAID: CA2580616050
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
7
Case#: Patient 7: Enrolled in study at 21.8 years, Female, onset at 2 years, diagnosed at 1.9 years, ERT started 19.6 years DiseaseAssertion:MPS1 S FamilyInfo: Consanguinity No CasePresentingHPOs:Corneal opacity (HP:0007957), Joint stiffness (HP:0001387), , CaseHPOFreeText: CaseNotHPOs: Macrocephaly (HP:0000256), Hepatosplenomegaly (HP:0001433)CaseNotHPOFreeText: CaseEnzymeAssay: CaseUrineGAGs: 2.13(min)-3.99(max) mg GAG/mmol creatinine while on ERT CaseERT: Laronidase dose-optimization trial : standard regimen – 0.58 mg/kg/week; biweekly regimen – 1.2 mg/kg every two weeks CaseBMT:Nil Variant1: IDUA W402X Variant1ClinVar ID: 11908 Variant1CAID: CA220498 Variant2: IDUA R383H Variant2ClinVarID: 558189 Variant2CAID: AdditionalVariants:Nil ParentalGenotype:NA PreviouslyPublishedNA
Case#: Patient 1, 9 years old, Iranian
DiseaseAssertion: MPSI-H (Severe)
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 0.12 µmol/g.h (Normal ranges: 10-50 µmol/g.h)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.469T>C (p.S157P)
Variant1ClinVarID: N/A
Variant1CAID: CA355961573
Variant2: c.469T>C (p.S157P)
Variant2ClinVarID: N/A
Variant2CAID: CA355961573
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Case#: Patient 4, Turkish
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.494-1G>A
Variant1ClinVarID: 557942
Variant1CAID: CA355961634
Variant2: c.494-1G>A
Variant2ClinVarID: 557942
Variant2CAID: CA355961634
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
PMID: 31298590
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
One boy
Case#: Patient 1, male, 15 months (age at diagnosis), 20.5 months (age at HSCT), weight of 12.7 kg (at HSCT), 5.8 years (age at report). Upon HSCT the patient made neurodevelopmental progress and attended kindergarten, he still had severe mental disabilities and aggressive behavior problems.
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Neurodevelopmental delay, speech delay, mild lumbar hyperlordosis (HP:0012758, HP:0000750, HP:0002938)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Activity of alpha-L-iduronidase in leukocytes was normal from 2 months after cessation of ERT.
CaseUrineGAGs: Patient had normal excretion of total urine GAGs.
CaseERT: Yes - 21 weeks of ERT before HSCT. Continued until day 107 of HSCT.
CaseBMT: Yes - interval diagnosis for HSCT (22 weeks). The donor was female and unrelated.
Variant1: c.208C>T (p.Q70X)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2: c.1205G>A (p.W402X)
Variant2ClinVarID: 11908
Variant2CAID: CA220498
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I
PMID: 21364962
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
MPS I_Case 05
Case#: MPS I_Case 05, female newborn
DiseaseAssertion: MPS type I, MPS I, MPS-I, attenuated MPS I
FamilyInfo: MPS I_Case 01 and MPS I_Case 05 are siblings
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText: This proband is believed to be an affected MPS-patient however, the proband did not have any obvious clinical symptoms to date (up to two years of age). The paper states that this attenuated MPS I case will need a long term follow up.
CaseEnzymeAssay: Proband identified by newborn screening. alpha-L-iduronidase activity in dried blood spot sample is 0.56 umole/L/Hr; this is below the study's DBS enzyme activity cutoff value of 3 umol/L/h
CaseUrineGAGs: Urine DMB GAG ratio is 65.7 mg/mmol creatinine. 4.76 ug/ml dermatan sulfate in urine (<0.41 ug/ml is the reference cutoff for dermatan sulfate in this study). 3.35 ug/ml heparan sulfate in urine (<0.8 ug/ml is the reference cutoff for heparan sulfate in this study). 0.17 ug/ml keratan sulfate in urine.
CaseERT: Don't know (would assume no since the proband is a newborn)
CaseBMT: Don't know (would assume no since the proband is a newborn)
Variant1: c.300–3C>G
Variant1ClinVarID: 551563
Variant1CAID: CA549265042
Variant2: c.1874A>C, p.Y625S
Variant2ClinVarID: 2910181
Variant2CAID: CA355965961
AdditionalVariants: No additional variants mentioned
ParentalGenotype: No parental testing results are available
PreviouslyPublished No statement from the author indicating the proband is previously published. Since this is a newborn study, I strongly believe this is the proband’s first time being published.
Case report: a rare case of Hunter syndrome (type II mucopolysaccharidosis) in a girl
PMID: 31046699
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
PMID: 22371174
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Hematopoietic stem cell transplantation improves the high incidence of neutralizing allo-antibodies observed in Hurler’s syndrome after pharmacological enzyme replacement therapy
PMID: 22371174
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
4 missense mutations
Case#: One patient from The Netherlands
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.979G>C (p.A327P)
Variant1ClinVarID: 167190
Variant1CAID: CA234128
Variant2: c.1205G>A (p.W402X)
Variant2ClinVarID: 11908
Variant2CAID: CA220498
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
P7
Case#: P7, Male, 0.9 years (diagnosed), 1.7 (report), 11 kg (weight), 78 cm (height), Algerian
DiseaseAssertion: Scheie Syndrome
FamilyInfo: Parents are consanguineous: P8 is a sibling of P7
CasePresentingHPOs: HP:0001999, HP:0002240, HP:0001387, HP:0007957 (Facial Dysmorphic Features, Hepatomegaly, Hernia(Ombelical), Corneal Opacity)
CaseHPOFreeText: Chronic Rhinorrhea, Cardiac Manifestations(Mitral Insufficiency & Aortic Insufficiency)
CaseNotHPOs: HP:0001249, HP:0000943, HP:0001387, HP:0000238 (Mental Retardation, Multiple Dysostosis, Joint Stiffness, Hydrocephalus)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA Enzyme activity 9 (% to the reference range mean)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Direct DNA Fragments Sequencing
Variant1: c.1598C>G (p.Pro533Arg)
Variant1ClinVarID: 11910
Variant1CAID: CA256112
Variant2: c.1598C>G (p.Pro533Arg)
Variant2ClinVarID: 11910
Variant2CAID: CA256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
patients
Case#: Patient 9, 9-years old at the start of ERT
DiseaseAssertion: MPS1-H/S - confirmed diagnosis of MPS 1 by enzymatic and mutation analysis
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: Urine GAGs are displayed in a figure and show the level at the start of ERT to 18-months later. At the start, urine GAGs appear to be close to 25 mg/mmol creatinine. After 18-months they decreased to be between 10-15 mg/mmol creatinine. Normal values for 2-10-year olds are 5-15 mg/mmol creatinine.
CaseERT: Yes - started at 9-years old and was given once every week
CaseBMT: No
Variant1: c.1205G>A (p.W402X)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: c.1513C>G (p.R505G)
Variant2ClinVarID: 1482722
Variant2CAID: CA355964784
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
c.314G>A
Case#: Functional assay variant with a clinical significance of benign.
DiseaseAssertion: MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.314G>A (p.R105Q)
Variant1ClinVarID: 92641
Variant1CAID: CA145881
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
c.246C>G
Case#: Functional assay variant with a clinical significance of clinically benign.
DiseaseAssertion: MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.246C>G (p.H82Q)
Variant1ClinVarID: 92637
Variant1CAID: CA220506
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
c.1598C>G
Case#: Functional assay variant with a clinical significance of pathogenic.
DiseaseAssertion: MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1598C>G (p.P533R)
Variant1ClinVarID: 11910
Variant1CAID: CA256112
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
c.99T>G
Case#: Functional assay variant with a clinical significance of benign.
DiseaseAssertion: MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.99T>G (p.H33Q)
Variant1ClinVarID: 92651
Variant1CAID: CA145894
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Case#: Patient is from The Netherlands
DiseaseAssertion: MPSI-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.653T>C (p.L218P)
Variant1ClinVarID: 222995
Variant1CAID: CA356986
Variant2: c.1205G>A (p.W402X)
Variant2ClinVarID: 11908
Variant2CAID: CA220498
AdditionalVariants: G387+6C>T on same allele
ParentalGenotype: N/A
PreviouslyPublished N/A
Pt5
Case#: Pt5, Female, 54 months (diagnosis), 24 months (onset)
DiseaseAssertion: Hurler Syndrome
FamilyInfo: N/A Pedigree (Figure 4Pt5)
CasePresentingHPOs: HP:0000280, HP:0007957, HP:0001387, HP:0000365, HP:0100814, (Coarse face, Cornea clouding, Joint stiffness, Hearing Loss, Dermal melanocytosis)
CaseHPOFreeText: N/A
CaseNotHPOs: HP:0001654, HP:0001433 (Valvular heart disease, Hepatosplenomegaly)
CaseNotHPOFreeText: Long bone deformation, Spinal Deformation, Inguinal or Umbilical hernia
CaseEnzymeAssay: α-L-iduronidase 0.43 (leukocytes, normal 15.9–41.8 nmol/mg prot/h)
CaseUrineGAGs: Urine glycosaminoglycans 508.8 (mg/g creatinine) {10.7-112}
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Not Provided.
Variant1: c.1190-10C>A
Variant1ClinVarID: 950888
Variant1CAID: CA1139658405
Variant2: c.1046A>G
Variant2ClinVarID: 950889
Variant2CAID: CA2802173
AdditionalVariants: N/A
ParentalGenotype: Female parent is heterozygous for c.1190-10C>A variant; Male Parent is heterozygous for c.1046A>G variant (figure 4 Pt5)
PreviouslyPublished: N/A
III
Case#: Patient III, origin of proband is Holland
DiseaseAssertion: Scheie syndrome (S)
FamilyInfo: No family information provided
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: 0.60 nmol/mghour IDUA enzyme activity in proband. Reference range of IDUA enzyme activity is 14.0 - 40.0 nmol/mghour
CaseUrineGAGs: Information not stated in this paper
CaseERT: Don't know
CaseBMT: Don't know
Variant1: c.1205G>A, p.W402X
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: Not identified in this study
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: No additional variants mentioned
ParentalGenotype: No parental information provided
PreviouslyPublished: I do not believe this proband was previously published. The paper states that variant "c.1205G>A have been found in patients previously." It does not link the variant to a specific paper but instead references a list of papers. Here are the PMIDs of those paper: 7951228, 1301196, 1301941, and 7550232
UNIGEi001-A
Case#:UNIGEi001-A, 2-year-old, Male, Caucasian, MPS1-H diagnosed by Division of Metabolism and Children's Research Center of University Children's Hospital of Zürich (Switzerland) DiseaseAssertion:MPS1-H FamilyInfo: N/A CasePresentingHPOs: N/A CaseHPOFreeText: N/A CaseNotHPOs: N/A CaseNotHPOFreeText: N/A CaseEnzymeAssay: N/A CaseUrineGAGs: N/A CaseERT: Don't know CaseBMT: Don't know Variant1: NM_000203.5(IDUA):c.1073_1093del (p.His358_Thr364del) Variant1ClinVarID: 557260 Variant1CAID: CA658823289 Variant2: NM_000203.4(IDUA):c.1205 G>A (p.Trp402Ter) Variant2ClinVarID: 11908 Variant2CAID: CA220498 AdditionalVariants: N/A ParentalGenotype: N/A PreviouslyPublished N/A
6
Case#: Patient 6, female, twin of Patient 5 (see Table 1)
DiseaseAssertion: MPS I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Low IDUA enzyme activity 0.75 (Ref. 4.87 ~ 54.70 μmol/g protein/h)
CaseUrineGAGs: Positive GAG tests
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1037T>G (p.L346R)
Variant1ClinVarID: 11927
Variant1CAID: CA256128
Variant2: c.1091C>T (p.T364M)
Variant2ClinVarID: 11925
Variant2CAID: CA256126
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
1
Case#: Infant #1, female
DiseaseAssertion: MPS I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Low IDUA enzyme activity 1.20 (Ref. 4.87 ~ 54.70 μmol/g protein/h)
CaseUrineGAGs: Negative GAG tests
CaseERT: N/A
CaseBMT: N/A
Variant1: c.2T>C (p.M1?)
Variant1ClinVarID: 639529
Variant1CAID: CA2801095
Variant2: c.343G>A (p.D115N)
Variant2ClinVarID: N/A
Variant2CAID: CA355961124
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
patient
Case#: Female, born at term via cesarean section. Birth weight was 3.850 (+0.93-SDS); length 50 cm (+0.2-SDS); cranial circumference: 36.8 cm (+1.1-SDS).
DiseaseAssertion: MPS-IH
FamilyInfo: Proband was born to unrelated parents.
CasePresentingHPOs: Congenital hip dysplasia (detected at 2 months), systolic murmur, hepatomegaly, macrocrania, coarse facial features, umbilical hernia, corneal clouding, mild thoracic and lumbar kyphosis (HP:0001385, HP:0031664, HP:0002240, HP:0000256, HP:0000256, HP:0001537, HP:0007957, HP:0002751)
CaseHPOFreeText: Frequent episodes of upper airway inflammation, neuro-motor delay, palpable liver, mitral dysplastic valve, thickened and prolapsing flaps with moderate mitral valve insufficiency. MRI of the brain showed dilated perivascular Virchow-Robin spaces, in the peritrigonal site bilaterally and in the corpus callosum, and a slightly dilated ventricular system in the supratentorial area. Slight tibial valgus. X-rays detected an altered coxo-femoral joint with lateralization of the femoral head.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Enzymatic activity of IDUA was undetectable.
CaseUrineGAGs: An increased amount of heparan and dermatan sulfate.
CaseERT: Yes, began at 23 months. 100U/kg laronidase (Aldurazyme) weekly dose. The patient presented recurrent febrile infections and disease progression (appearance of cornea opalescence).
CaseBMT: Yes, UCB-HSCT & MUD-HSCT. First allo- HSCT from unrelated cord-blood-derived stem cells was at the age of 27 months. Six months later (33 months of age), she underwent a second HSCT from an HLA-matched unrelated donor. Normal IDUA activity was reported about 30 days post HSCT and progressively decreasing urinary GAG.
Variant1: c.152G>A (p.G51D)
Variant1ClinVarID: 193061
Variant1CAID: CA274902
Variant2: c.1598C>G (p.P533R)
Variant2ClinVarID: 11910
Variant2CAID: CA256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Patient 2
Case#: Patient 2, Chinese descent, 9 years old (age at report), height of 95 cm (3rd percentile), weight of 22.5 kg (35th percentile)
DiseaseAssertion: MPS 1
FamilyInfo: The second child of non-consanguineous parents. Affected younger sister (Patient 1).
CasePresentingHPOs: Short stature, skeletal dysplasia, joint stiffness, claw hand deformity, coarse facial features, prominent forehead, wide nose, flared nostrils, thick lips, inguinal hernia, visual impairment, endocardial fibroelastosis, asthma (HP:0004322, HP:0002652, HP:0001387, HP:0034337, HP:0000280, HP:0011220, HP:0000445, HP:0000454, HP:0000219, HP:0000023, HP:0000505, HP:0001706, HP:0002099)
CaseHPOFreeText: Fulminant myocarditis, minor mitral, tricuspid, aortic, and pulmonary regurgitation (at 8 months of age), edema and granular opacity of the corneas
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.2T>C (p.M1?)
Variant1ClinVarID: 639529
Variant1CAID: CA2801095
Variant2: c.911delT (p.V304fs)
Variant2ClinVarID: 1184991
Variant2CAID: CA2573052265
AdditionalVariants: N/A
ParentalGenotype: Paternal: c.2T>C, Maternal: c.911delT
PreviouslyPublished N/A
10 MPS I patients
Case#: MPS 1 patient
DiseaseAssertion: N/A
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1139A>G (p.Q380R)
Variant1ClinVarID: 550779
Variant1CAID: CA2802202
Variant2: c.1139A>G (p.Q380R)
Variant2ClinVarID: 550779
Variant2CAID: CA2802202
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
3
Case#: Patient 3 was biochemically diagnosed with MPS I because they showed an increase in urinary GAGs and a reduction in IDUA activity in leukocytes. Patient 3 was diagnosed at 2 years.
DiseaseAssertion: MPSI-H/S
FamilyInfo: N/A
CasePresentingHPOs: Coarse facies, corneal clouding, skeletal abnormalities (HP:0000256, HP:0007957, HP:0002360)
CaseHPOFreeText: N/A
CaseNotHPOs: Cardiac abnormalities, hepatosplenomegaly, intellectual disability, growth delay, hernias (HP:0001627, HP:0001433, HP:0001249, HP:0001510, HP:0100790)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA activity of 5.9 nmol/mg/protein/hr. No reference range provided.
CaseUrineGAGs: 2439.5 CPC unit/g creatinine. No reference range provided.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.613_617dup (p.E207Afs*29)
Variant1ClinVarID: 11921
Variant1CAID: CA256123
Variant2: c.1591delC (p.R531Gfs*29)
Variant2ClinVarID: 556184
Variant2CAID: CA658823295
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
One patient was heterozygous for c.399G>C (p.M133I), c.606C>A (p.Y202X) and c.208C>T (p.Q70X). Although parental samples were not provided for this proband, the p.M133I and p.Y202X changes have previously been reported to be in cis in another patient (Matte et al 2003)
Case#: Unlabeled Patient
DiseaseAssertion: MPS 1
FamilyInfo: n/a
CasePresentingHPOs: n/a
CaseHPOFreeText: n/a
CaseNotHPOs:
CaseNotHPOFreeText:
GenotypingMethod: All coding exons of IDUA plus at least 25 base-pairs of flanking intronic sequence were amplified by polymerase chain reaction (PCR). PCR fragments were sequenced using a standard protocol and run on an Applied Biosystems DNA analyzer (3100, 3130, or 3730xl).
PreviouslyPublished: no
Variant: NM_000203.3 c.399G>C (p.M133I), c.606C>A (p.Y202X) and c.208C>T (p.Q70X) phase unknown
CAID: CA355961907
SupplementalData: n/a
11
Case#: Patient 11, male, age of diagnosis is 11 months
DiseaseAssertion: Mucopolysaccharidosis type I, MPS-I, Maternal Mucopolysaccharidosis type I
FamilyInfo: No family information provided in this paper
CasePresentingHPOs:
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText:
CaseEnzymeAssay: No results of iduronidase enzyme assay mentioned in this paper
CaseUrineGAGs: No record/details of urine GAG levels in this paper
CaseERT: Don't know
CaseBMT: Don't know
Variant1: c.208 C>T (p.Gln70*)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2: c.208 C>T (p.Gln70*)
Variant2ClinVarID: 11909
Variant2CAID: CA204563
AdditionalVariants: No additional variants mentioned in this paper
ParentalGenotype: Variant of proband is from his mother; "11-month-old boy with a homozygous nonsense variant, c.208C>T (p.Gln70*), in exon 2 of IDUA, resulting from UPD(4)mat of 18 Mb on chromosome 4 pter."
PreviouslyPublished: Author states that he found this patient from 30737479 (PMID).
10
Case#: Patient 10 (see Table 2), male, 25.5 years old (age at report), 7 years (duration of treatment), 12 surgeries
DiseaseAssertion: MPS1-HS
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: HP:0000238, HP:0002176, HP:0002360 (Hydrocephalus, spinal cord compression, sleep abnormality)
CaseNotHPOFreeText: Shunt placement, psychiatric problems
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes
CaseBMT: N/A
Variant1: c.1598C>G (p.P533R)
Variant1ClinVarID: ClinVarID:11910
Variant1CAID: CA256112
Variant2: c.1598C>G (p.P533R)
Variant2ClinVarID: 11910
Variant2CAID: CAID:CA256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Neurocognitive and neuropsychiatric phenotypes associated with the mutation L238Q of the alpha-L-iduronidase gene in Hurler-Scheie syndrome
PMID: 24368159
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Case#: 11 years old (age of onset). The patient became pregnant at 30 years of age and had one miscarriage at 17 weeks. 7 months later, she went on to deliver a healthy male at 37 weeks. The boy, now 2.5 years old, has continued to develop normally.
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: Carpal tunnel syndrome, joint stiffness, limitation of joint mobility (HP:0012185, HP:0001387, HP:0001376)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes - initiation of ERT with laronidase (100 U/kg/week) when she was 30-years-old
CaseBMT: N/A
Variant1: c.979G>C (p.A327P)
Variant1ClinVarID: 167190
Variant1CAID: CA234128
Variant2: c.886_887ins12 (12-base pair in-frame insertion at position 886 of iduronidase cDNA). Unclear which 4 amino acids are being inserted into this region.
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Patient 4
Case#: Patient 4, Male, 1 year 8 months (diagnosed), 3 years (report), Deceased, Bizerte (Tunisian origin)
DiseaseAssertion: N/A
FamilyInfo: Parents are consanguineous between 1st cousins
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Leukocyte IDUA activity <0.1% (% normal) ; determined in sonicated leukocyte pellets using the artificial substrate 4-methylumbellifery IDUA
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sequencing exons and intro-exon junctions; Phenol/chloroform procedure
Variant1: p.L530fs (c.1587_1588insGC)
Variant1ClinVarID: N/A
Variant1CAID: CA2580611004
Variant2: p.L530fs (c.1587_1588insGC)
Variant2ClinVarID: N/A
Variant2CAID: CA2580611004
AdditionalVariants: p.H33Q (c.99 T > G), p.R105Q (c.314G > A), p.N181N (c.543 T > C), IVS5-45 (c.590-45) G > C), IVS5-8 (c.590-8C > T), p.A314A (c.942G > C), IVS7+48(c.972+48A > G), IVS745(c.973- 45G > C), p.A361T (c.1081G > A), p.T388T (c.1164G > C), p.V454I (c.1360G > A), IVS9+36 (c.1402+36T > C), p.R489R (c.1467C > T), IVS12+72 (c.1727T > G)
ParentalGenotype: N/A
PreviouslyPublished N/A
Patient 1
Case#: Patient 1, Female, 2 years 5 days (diagnosed), 9 years (report), Makthar (Tunisian origin)
DiseaseAssertion: Hurler Syndrome
FamilyInfo: Parents are consanguineous between 3rd cousins
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Leukocyte IDUA activity 0.1% (% normal) ; determined in sonicated leukocyte pellets using the artificial substrate 4-methylumbellifery IDUA
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sequencing exons and intro-exon junctions; Phenol/chloroform procedure
Variant1: p.Y581X
Variant1ClinVarID: 550883
Variant1CAID: CA2802392
Variant2: p.Y581X
Variant2ClinVarID:550883
Variant2CAID: CA2802392
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Scheie
Case#: Patient 13 (group 2), Poland, male 2 years old (age at diagnosis), 2.5 years old (age at baseline), 6.5 years old (current age)
DiseaseAssertion: MPS1-S
FamilyInfo: N/A
CasePresentingHPOs: Limitation of join mobility, joint stiffness (HP:0001376, HP:0001387)
CaseHPOFreeText: Patients in group 2 had normal mental development or only slightly delayed mental development and, therefore, could undergo active physical rehabilitation.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Diagnosis of MPS I was confirmed by the biochemical determination of α-L-iduronidase activity deficiency in leukocytes and by molecular analysis.
CaseUrineGAGs: N/A
CaseERT: Yes, weekly infusions for 52-208 weeks (depending on the patient)
CaseBMT: N/A
Variant1: c.208C>T (p.Q70X)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2: c.227A>G (p.Y76C)
Variant2ClinVarID: 552686
Variant2CAID: CA2801140
AdditionalVariants: Yes - c.1345C>A (p.H449N), ClinVarID:350230, CAID:CA2802233
ParentalGenotype: N/A
PreviouslyPublished N/A
6/M
Case#: 6, Male, 1 month (onset), 18 months (diagnosed), 18 months (report)
DiseaseAssertion: Hurler Syndrome
FamilyInfo: Not Provided
CasePresentingHPOs: HP:0001387, HP:0002240, HP:0000501, HP:0000280, HP:0000943, HP:0007957 (Joint Stiffness, Hepatomegaly (moderate), Glaucoma, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)
CaseHPOFreeText: (Mental Development (delayed since 1y), LV hypertrophy (at 3y), Inguinal bilat. and umbilical hernia)
CaseNotHPOs: HP:0001744 (Splenomegaly)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Not Provided
Variant1: p.W402X (not identified)
Variant1ClinVarID: 11908
Variant1CAID: CA220498
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: p.A8, p.A20, p.N297
ParentalGenotype: N/A
PreviouslyPublished N/A
21/M
Case#: 21, Male, 1 month (onset), 1 month (diagnosed), 12 months (report)
DiseaseAssertion: Hurler Syndrome
FamilyInfo: N/A
CasePresentingHPOs: HP:0002240, HP:0000280, HP:0000943, HP:0007957 (Hepatomegaly (mild at diagnosis and none at 12m), Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)
CaseHPOFreeText: (Mental Development (delayed since infancy), Mild LV hypertrophy, Inguinal bilat. and Umbilical Hernia)
CaseNotHPOs: HP:0001387, HP:0001744 (Joint Stiffness, Splenomegaly)
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Not Provided
Variant1: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Patient 2
Case#:1.1 year female, diagnosed at 0.9 years DiseaseAssertion:MPS1H FamilyInfo:NA CasePresentingHPOs:NA CaseHPOFreeText:NA CaseNotHPOs:NA CaseNotHPOFreeText:NA CaseEnzymeAssay:Undetectable CaseUrineGAGs:NA CaseERT:NA CaseBMT:Yes, Unrelated cord blood, Post HSCT 2.7 nmol/h/mg of protein ( α-l-Iduronidase Levels) Variant1:IDUA : c.1087C>T Variant1ClinVarID:557205 Variant1CAID:CA2802184 Variant2:IDUA: c.1205G>A Variant2ClinVarID: 11908 Variant2CAID:CA220498 AdditionalVariants: ParentalGenotype: PreviouslyPublished
5
Case#: Patient 5 (see Table 1), 10 years (age at report), 8 months (age at onset), male, height of 118 cm, weight of 18 kg, location at Gabes: Industrial region.
DiseaseAssertion: MPS1 - severe
FamilyInfo: One affected siblings (Patient 4), parents were 1st cousins (see Table 2) aged 55 yrs (M) and 65 yrs (F).
CasePresentingHPOs: HP:0004322, HP:0001999, HP:0000924, HP:0007957, HP:0001537, HP:0010864 (Short stature, abnormal facial shape, skeletal abnormality, corneal clouding, umbilical hernia, severe intellectual disability)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA activity: 0.018 μKat/kg
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1598C>G (p.P533R)
Variant1ClinVarID: 11910
Variant1CAID: CA:256112
Variant2: c.1598C>G (p.P533R)
Variant2ClinVarID: 11910
Variant2CAID: CA:256112
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
MPS-I fibroblasts had a stop codon on both alleles of the iduronidase gene, causing a truncated protein p.W402X,
Case#:1 (it is unclear whether the fibroblasts carrying these variants were derived from a single or multiple patients).
DiseaseAssertion: MPS-I
FamilyInfo: not provided
CasePresentingHPO: not provided
CaseHPOFreeText: not provided
CaseNotHPO: not provided
**CaseNotHPOFreeText: not provided
CaseEnzymeAssay:fibroblast iduronidase activity reported but not clear if results are for a single or multiple patients
CaseUrineGAGs: not provided
CaseERT:" Don't know
CaseBMT:Dont' know
Variant1: p.W402X
Variant1ClinVarID: 11908
Variant2: p.W402X
Variant2ClinVarID: 11908
AdditionalVariants: none noted
ParentalGenotypes: not provided
PreviouslyPublished: not specified
T1-2
Case: T1-2, female, 52yo
DiseaseAssertion: VWD1
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs:
CaseHPOFreeText: Blood type: O+, bleeding score = 12, VWF:Ag (IU/mL) = 0.14; VWF:RCo (IU/mL) = 0.13; FVIII:C (IU/mL) = 0.46
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: qRT-PCR
PreviouslyPublished:
Gene: VWF
Variant: c.221-977_532+7059del
HGVS: NM_000552.5(VWF):c.221-977_532+7059del
ClinVarID: 156329; https://www.ncbi.nlm.nih.gov/clinvar/variation/156329/?oq=c.221-977_532+7059del&m=NM_000552.5(VWF):c.221-977_532%207059del
CAID: n/a
gnomAD: absent
P2
Case: P2, F/42
DiseaseAssertion: VWD3
FamilyInfo: No
ParentalGenotype: NA
CaseHPOFreeText: The bleeding score was 12, aPTT was 58 seconds, FVIII:C was 7%, VWF:RCo was 6 IU/dL, and VWF:Ag was not determined. The VWF:RCo/VWF:Ag ratio was not available. RIPA was nearly absent, VWF multimer analysis was 2, and platelet count was 231 × 10⁹/L.
CasePreviousTesting: NA
GenotypingMethod: Direct sequencing of all exons, flanking intronic sequences, and the promoter of VWF was performed.
Gene: VWF
Variant: no mutation detected
HGVS:
ClinVar:
CAID:
gnomAD:
P7
Case: P7, M/41
DiseaseAssertion: VWD2A
FamilyInfo: Positive family history, no details provided.
ParentalGenotype: NA
CaseHPOFreeText: The bleeding score was 7, aPTT was 36 seconds, FVIII:C was 36%, VWF:RCo was not determined, and VWF:Ag was 25 IU/dL. The VWF:RCo/VWF:Ag ratio was not applicable. The VWF multimer pattern showed a mild loss of high molecular weight multimers, RIPA was 4 ohms, and the platelet count was 301 × 10⁹/L.
CasePreviousTesting: NA
GenotypingMethod: Direct sequencing of all exons, flanking intronic sequences, and the promoter of VWF was performed.
Gene: VWF
Variant: c.4789C>T, p.R1597W — heterozygous
HGVS: NM_000552.5(VWF):c.4789C>T (p.Arg1597Trp)
ClinVar: 285
CAID: CA114117
gnomAD: https://gnomad.broadinstitute.org/variant/chr12-6018629-G-A?dataset=gnomad_r4
Case: Patient D
DiseaseAssertion: VWD2N
FamilyInfo: Family 3
ParentalGenotype(s):
CasePresentingHPOs: HP:0012147, HP:0030129, HP:0030130, HP:0011871
CaseHPOFreeText: PTsec = 37.9, FVIII U/dL = 31.1, FVIII ratio = 0.33, VWF:Ag U/dL = 95.0, VWF:FVIIIB U/dL = 23.8, VWF:FVIIIB ratio = 0.25, VWF:CB U/dL = 101.6, VWF:RCo U/dL = 112.4, RIPA % = 73.4, PlatVWF:Ag U/dL = 87.2
CaseNOTHPOs:
CaseNOTHPOFreeText: n/a
CasePreviousTesting: n/a
GenotypingMethod: "Genetic analysis was performed on exons 17-20 of the VWF gene as previously described" (PMID: 12393698)
PreviouslyPublished: n/a
Gene: VWF
Variant: c.2561G>A (p.Arg854Gln); homozygous
HGVS: NM_000552.5(VWF):c.2561G>A (p.Arg854Gln)
ClinVarID: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/?new_evidence=false
CAID: n/a
gnomAD: MAF (European, Finnish) = 0.005692; https://gnomad.broadinstitute.org/variant/12-6143978-C-T
10 F/56 <1 6 No NA c.4645G>Ta/c.7344C>Aa p.E1549Xa/p.C2448Xa 28/43 Heterozygous
Case: 10, F, 56, Italian
DiseaseAssertion: VWD type 3
FamilyInfo: Consanguinity: no
ParentalGenotype: n/a
CasePresentingHPOs: n/a
CaseHPOFreeText: VWF:Ag (IU/dL): <1, FVIII:C (IU/dL): 6, Bleeding Score: n/a
CaseNotHPOs: n/a
CaseNotHPOFreeText: Anti-VWF alloantibodies: no
CasePreviousTesting: n/a
Gene: VWF
Variant:
c.4645G>T (p.Glu1549X), Exon 28
c.7344C>A (p.Cys2448X), Exon 43
Compound Heterozygous
5
Case: Patient 5 (Family B), male, 26yo
DiseaseAssertion: VWD2B
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0030132, HP:0030129, HP:0030130, HP:0011871, HP:0012147
(Absence of large von Willebrand factor multimers, impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)
CaseHPOFreeText: blood group O, Platelet count x103/μl = 176, PFA 100 sec = >300, SPA % = 8, MADR mg/mL = 0.6, VWF:Ag U/dL = 17.6, VWF:CB U/dL = 9.2, VWF:CB ratio = 0.52, VWF:RCo U/dL = 10.4, VWF:RCo ratio = 0.59, Platelet VWF U/dL = 76.6, FVIII U/dL = 38.8, BAT F/M = 8
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: Sequencing of exon 28 of VWF
PreviouslyPublished: NA
Gene: VWF
Variant: c.3922C>T (p.Arg1308Cys)
HGVS: NM_000552.4(VWF):c.3922C>T (p.Arg1308Cys)
ClinVarID: 289; https://www.ncbi.nlm.nih.gov/clinvar/variation/289/
CAID: NA
gnomAD: absent
19
Case: Patient 19 (Family F), male, 44yo
DiseaseAssertion: VWD2B
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0030132, HP:0030129, HP:0030130, HP:0011871, HP:0012147
(Absence of large von Willebrand factor multimers, impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)
CaseHPOFreeText: blood group O, Platelet count x103/μl = 116, PFA 100 sec = >300, SPA % = 15.7, MADR mg/mL = 0.3, VWF:Ag U/dL = 44.7, VWF:CB U/dL = 11.8, VWF:CB ratio = 0.48, VWF:RCo U/dL = 11.4, VWF:RCo ratio = 0.71, Platelet VWF U/dL = 130, FVIII U/dL = 27.7, BAT F/M = 10
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: Sequencing of exon 28 of VWF
PreviouslyPublished: NA
Gene: VWF
Variant: c.3916C>T (p.Arg1306Trp)
HGVS: NM_000552.4(VWF):c.3916C>T (p.Arg1306Trp)
ClinVarID: 288; https://www.ncbi.nlm.nih.gov/clinvar/variation/288/
CAID: NA
gnomAD: absent
I : 3
Case#: F4, I:3
DiseaseAssertion: Type 2 VWD
CaseHPOFreeText: all mutimers present, VWF:Ag = 34; VWF:RCo = 21; VWF:GPIbM = 31; 0.62; 0.92; 1.49
CasePreviousTesting: Not clearly described
Gene: VWF
Variant: p.[R1308L];[=]
HGVS: c.3923G>T (p.Arg1308Leu)
CAID: CA6402650
gnomAD: https://gnomad.broadinstitute.org/variant/12-6019495-C-A?dataset=gnomad_r4
I : 2
Case#: F4, I:2
DiseaseAssertion: Type 2 VWD
CaseHPOFreeText: all mutimers present, VWF:Ag = 40; VWF:RCo = 25; VWF:GPIbM = 38; 0.63; 0.95; 1.52
CasePreviousTesting: Not clearly described
Gene: VWF
Variant: p.[R1308L];[=]
HGVS: c.3923G>T (p.Arg1308Leu)
CAID: CA6402650
gnomAD: https://gnomad.broadinstitute.org/variant/12-6019495-C-A?dataset=gnomad_r4
II : 1
Case#: F3, II:1
DiseaseAssertion: Type 2 VWD
CaseHPOFreeText: all mutimers present, VWF:Ag = 45; VWF:RCo = 38; VWF:GPIbM = 45; 0.84; 1.00; 1.19
CasePreviousTesting: Not clearly described
Gene: VWF
Variant: p.[P1266L];[=]
HGVS: NM_000552.5(VWF):c.3797C>T (p.Pro1266Leu)
CAID: CA114170
gnomAD: https://gnomad.broadinstitute.org/variant/12-6019621-G-A?dataset=gnomad_r4
Common large partial VWF gene deletion does not cause alloantibody formation in the Hungarian type 3 von Willebrand disease population
PMID: 21362127 Gene: von Willebrand factor HGNCID: 12726
193< 1< 13−−20Mc.241A>G/c.5315insGAp.R81G/p.D1772EfsX114/3116/17N/N
Case: Patient 19, M, Hungarian
DiseaseAssertion: VWD type 3
FamilyInfo: compatible with recessive inheritance
ParentalGenotype(s): n/a
CasePresentingHPOs: n/a
CaseHPOFreeRext: Bleeding score: 20, VWF:Ag (IU dL−1): < 1, VWF:CB (IU dL−1): < 1, FVIII:C (IU dL−1): 3, VWF:RCo below detection limit (<10 IU dL−1), not detectable VWF on multimer gels
CaseNOTHPOs: n/a
CaseNOTHPOFreeText: no inhibitor detected, did not become refractory to factor replacement therapy
CasePreviousTesting: n/a
Gene: VWF
Variant:
c.241A>G (p.Arg81Gly), Exon 4
c.5315insGA (p.Asp1772GlufsX11), Exon 31
Intron 40 VNTR 16/17
Note: multimer electrophoresis, Recombinant VWF antigen concentrations and Collagen binding activity (VWF:CB) measured by ELISA, direct sequencing of the 51 exons and the exon‐intron boundaries, Breakpoint analysis and breakpoint‐specific PCR
78 14 F 28 c.4525A.G p.I1509V Htz ,1 ,1 18 - -
Case: 78, F, 14 years, Indian
DiseaseAssertion: VWD type 3
FamilyInfo: no family history of disease, Consanguinity: no
ParentalGenotype: n/a
CasePresentingHPOs: n/a
CaseHPOFreeText: FVIII:C: (U/dl): <1, VWF:Ag (U/dl): <1, Bleeding Score: 18
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
CasePreviousTesting: n/a
Gene: VWF
Variant:
c.4525A>G (p.Ile1509Val), Exon 28
Heterozygous
83 13 M 15 c.1812C.A p.Y604* Hmz 2 ,1 6 - -
Case: 83, M, 13 years, Indian
DiseaseAssertion: VWD type 3
FamilyInfo: Consanguinity: no, no family history of disease
ParentalGenotype: n/a
CasePresentingHPOs: n/a
CaseHPOFreeText: FVIII:C: (U/dl): 2, VWF:Ag (U/dl): <1, Bleeding Score: 6
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
CasePreviousTesting: n/a
Gene: VWF
Variant:
c.1812C>A (p.Tyr604*), Exon 15, Homozygous
T058F/1n/a0.010.030.02c.2443-?_2685 + ?del, c.5180_5181insTTp.Val815_Gln895del p.Leu1727 fs19–20/30Compound heterozygous
Case: T058, F, 1
DiseaseAssertion: VWD type 3
FamilyInfo: insertion mutation was inherited from the father and the partial gene deletion from the mother
CasePresentingHPOs: n/a
CaseHPOFreeText: VWF:Ag (IU/ml): 0.01, VWF:RCo (IU/ml): 0.03, FVIII:C (IU/ml): 0.02
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
CasePreviousTesting: n/a
Gene: VWF
Variant:
c.2443-?_2685 + ?del (p.Val815_Gln895del), Exon 19-20
c.5180_5181insTT (p.Leu1727 fs), Exon 30
Compound heterozygous
Note: ELISA-based assay for detecting alloantibodies, genomic analysis via sequencing of leukocytes for the VWF gene including exons 1-52 and about 1.5 km of VWF promoter, PCR amplification for variant confirmation, SALSA-MLPAVWF assay evaluation for partial/total gene deletions when sequencing did not reveal pathogenic explanation
26IranM/24<1—YesSevere7683delTFS45HomozygousEco57 I (+)
Case: 26, M, 24, Iranian
DiseaseAssertion: VWD type 3
FamilyInfo: Consanguinity: Yes
ParentalGenotype: n/a
CasePresentingHPOs: n/a
CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe
CaseNotHPOs: n/a
CaseNotHPOFreeText: Anti-VWF alloantibodies: no
CasePreviousTesting: n/a
Gene: VWF
Variant:
7683delT (FS), Exon 45, Homozygous
19*IranF/112—YesSevere2116C→TQ706X16HomozygousBsrI (−)
Case: 19, F, 11, Iranian
DiseaseAssertion: VWD type 3
FamilyInfo: Consanguinity: Yes
ParentalGenotype: n/a
CasePresentingHPOs: n/a
CaseHPOFreeText: VWF:Ag (U/dl): 2, Bleeding symptoms: Severe
CaseNotHPOs: n/a
CaseNotHPOFreeText: Anti-VWF alloantibodies: no
CasePreviousTesting: n/a
Gene: VWF
Variant:
2116C→T (Gln706X), Exon 16, Homozygous
20IranF/20<1—YesSevere3931C→TQ1311X28HomozygousBfaI (+)
Case: 20, F, 20, Iranian
DiseaseAssertion: VWD type 3
FamilyInfo: Consanguinity: Yes
ParentalGenotype: n/a
CasePresentingHPOs: n/a
CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe
CaseNotHPOs: n/a
CaseNotHPOFreeText: Anti-VWF alloantibodies: no
CasePreviousTesting: n/a
Gene: VWF
Variant:
3931C→T (Gln1311X), Exon 28, Homozygous
3951C→T (Ala1317Ala)
Note: Mutation Gln1311X is likely due to a gene conversion; both mutations match the pseudogene sequence
C1190R
Variant: p.Cys1190Arg and 5'UTR variant - VWF:Ag 32 IU/dL, VWF:RCo 29 IU/dL, FVIII:C 46 IU/dL -- patient also carries a promoter variant phase unknown, no bleeding phenotype or multimer data. First report of the variant
CA228423
43 U
Case: Patient 43, Family U (Table 1.), M/10, Afro-Caribbean
DiseaseAssertion: VWD2M
FamilyInfo: Patient 44 (M/15, Afro-Caribbean), Patient 46 (M/47, Afro-Caribbean, Patient 47(M/78, Afro-Caribbean) and Patient 48 (M/43, Afro Caribbean) also from Family U. (Table 1.)
ParentalGenotype(s): NA
CasePresentingHPOs:
CaseHPOFreeRext: BAT = 0, FVIII:C (IU/dL) = 71, VWF:Ag (IU/dL) = 30, VWF:Act (IU/dL) = 40
CaseNOTHPOs:
CaseNOTHPOFreeText: Blood group B+
CasePreviousTesting:
GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
PreviouslyPublished: NA
Gene: VWF
Variant: c.3943C > T p.(Arg1315Cys)
HGVS: NM_000552.5:c.3943C>T (p.Arg1315Cys)
ClinVarID: 100310
CAID: CA228502
gnomAD: MAF of 8.476e-7 (1/ 1179850 alleles) in European population https://gnomad.broadinstitute.org/variant/chr12-6019161-A-C?dataset=gnomad_r4
Variant: c.4138A > G, p.(Ile1380Val)
HGVS: NM_000552.5:c.4138A>G (p.Ile1380Val)
ClinVarID: 310063
CAID: CA6402595
gnomAD: MAF of 0.1184 (8878/74958 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019280-T-C?dataset=gnomad_r4
Variant: c.4304A > G, p.(Asn1435Ser)
HGVS: NM_000552.5:c.4304A>G (p.Asn1435Ser)
ClinVarID: 310062
CAID: CA6402552
gnomAD: MAF of 0.1124 (8427/74964 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019114-T-C?dataset=gnomad_r4
Variant: c.4414G > C p.(Asp1472His)
HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
ClinVarID: 256679
CAID: CA6402534
gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
37 R
Case: Patient 37, Family R (Table 1.), M/20, Afro-Caribbean
DiseaseAssertion: VWD2A (IIE)
FamilyInfo: Patient 36 (M/22, Afro-Caribbean) and Patient 38 (F/51, Afro-Caribbean) also from Family R. (Table 1.)
ParentalGenotype(s): NA
CasePresentingHPOs:
CaseHPOFreeRext: BAT = 1, FVIII:C (IU/dL) = 23, VWF:Ag (IU/dL) = 10, VWF:Act (IU/dL) = 10
CaseNOTHPOs:
CaseNOTHPOFreeText: Blood group O+
CasePreviousTesting:
GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
PreviouslyPublished: NA
Gene: VWF
Variant: c.1530G > A, p.(Val510 =) p.
HGVS: NM_000552.5:c.1530G>A (p.Val510=)
ClinVarID:
CAID: CA6403368
gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
Variant: c.1892C > T, p.(Ala631Val)
HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
ClinVarID: 422844
CAID: CA6403245
gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
Variant: c.2220G > A, p.(Met740Ile)
HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
ClinVarID: 100206
CAID: CA201316
gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
Variant: c.2451T > A, p.(His817Gln)
HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
ClinVarID: 100224
CAID: CA228345
gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
Variant: c.3445T > C, p.(Cys1149Arg)
HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
ClinVarID: 309
CAID: CA228410
gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
Variant: c.4414G > C p.(Asp1472His)
HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
ClinVarID: 256679
CAID: CA6402534
gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
Variant: c.6554G > A, p.(Arg2185Gln)
HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
ClinVarID: 100443
CAID: CA228748
gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
Identification and characterization of the elusive mutation causing the historical von Willebrand Disease type IIC Miami
PMID: 27344059 Gene: VWF HGNCID: HGNC:12726
Case: P1,Chinese, female, 17yo
DiseaseAssertion: VWD1
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type O blood, bleeding score = 8; VWF:Ag (%) = 38.0, VWF:RCo (%) = 35.2, FVIII:C (%) = 59.0, VWF:CB (%) = 33.2, VWFpp (%) = 52.9, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.9, VWFpp/VWF:Ag = 1.4, FVIII:C/VWF:Ag = 1.6
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.6860G>A (p.Arg2287Gln)
HGVS: NM_000552.3:c.6860G>A (p.Arg2287Gln)
ClinVarID: NA
CAID: CA6401877; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA6401877
gnomAD: MAF = 0.005415 (108/19946 alleles) in the East Asian population; https://gnomad.broadinstitute.org/variant/12-6094770-C-T
Case: P41, Chinese, female, 13yo
DiseaseAssertion: VWD3
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type A blood, bleeding score = 18; VWF:Ag (%) = 1.6, VWF:RCo (%) = 1.5, FVIII:C (%) = 2.8, VWF:CB (%) = 1.7, VWFpp (%) = 1.3, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 1.1, VWFpp/VWF:Ag = 0.8, FVIII:C/VWF:Ag = 1.8
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.2547-13T>A - Unregistered Variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Case: P55, Chinese, female, 24yo
DiseaseAssertion: VWD2A
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type O blood, bleeding score = 8; VWF:Ag (%) = 35.2, VWF:RCo (%) = 14.5, FVIII:C (%) = 57.9, VWF:CB (%) = 6.5, VWFpp (%) = 21.5, VWF:RCo/VWF:Ag = 0.4, VWF:CB/VWF:Ag = 0.2, VWFpp/VWF:Ag = 0.6, FVIII:C/VWF:Ag = 1.6
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant 1: c.1099T>G (p.Cys367Gly)
HGVS: NM_000552.5:c.1099T>G (p.Cys367Gly)
ClinVarID: NA
CAID: CA383505165; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383505165
gnomAD: absent
Variant 2: c.1450_1451delinsAG (p.His484Se) - Unregisted Variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Variant 3: c.2423G>A (p.Cys808Tyr)
HGVS: NM_000552.5:c.2423G>A (p.Cys808Tyr)
ClinVarID: NA
CAID: CA383521928; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383521928
gnomAD: absent
Homozygous type 2N R854W von Willebrand factor is poorly secreted and causes a severe von Willebrand disease phenotype
PMID: 20586924
Gene: VWF
HGNC: 12726
Disease: von Willebrand Disease Type 2N
MONDO: 0015631
InheritancePattern: Autosomal Recessive
Prevalence: Various sources (PMID: 28847738, PMID:19809303, PMID:29115006) can be combined to estimate the prevalence of VWD Type 2N between 1:15,000 and 1:80,000.
Penetrance: VWD type 2 is fully penetrant / nearly fully penetrant for most pathogenic variants.
IV-3
Case: Patient IV-3 (son of III-3; first cousin of proband's mother IV-4) DiseaseAssertion: Type 2A VWD, based on low plasma VWF:Ag and activity and lack of plasma HMW VWF multimers. FamilyInfo: Son of III-3 (proband's granduncle); first cousin of IV-4 (proband's mother); part of 5-affected-member pedigree (Fig. 1). ParentalGenotype(s): Father (III-3) heterozygous for the variant, affected. Mother's genotype not reported. CasePresentingHPOs: HP:0012147 (Reduced quantity of VWF; VWF:Ag 19.5 U/dL), HP:0030129 (Impaired VWF:RCo; VWF:Rco 7.6 U/dL), HP:0030132 (Absence of large VWF multimers — plasma), HP:0003645 (Prolonged partial thromboplastin time; APTT 45.2 sec) CaseHPOFreeText: Described only generically as having "abnormal bleedings" / "similar clinical symptoms" — no itemized bleeding symptoms given specifically for this individual. FVIII:C 29.0 U/dL (nv 50-150). RIPA not tested (N/A). TT 18.6 sec and PT 13.4 sec both within normal range. CaseNOTHPOs: NA CaseNOTHPOFreeText: Platelet-associated VWF multimers normal (HMW multimers present) per the group finding covering this patient. CasePreviousTesting: Targeted confirmation of the familial VWF variant; not genome-wide. GenotypingMethod: Sanger sequencing/allele-specific analysis, same platform as proband. PreviouslyPublished: NA Gene: VWF Variant: Same novel heterozygous in-frame 6-bp deletion, exon 28, ΔD1529V1530 (VWF A2 domain) HGVS: c.4585_4590del (p.Asp1529_Val1530del) ClinVarID: NA CAID: NA gnomAD: NA
39 U c.4943C > T N p.Pro1648Leu 28 A2 htz Missense A 59 55 57
Case: IP #39 in type U VWD sub-cohort (also in row 23 table 6)
DiseaseAssertion: unclassified VWD
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: HP:0032370 - blood group A
CaseHPOFreeRext: VWF:Ag [IU/dL] = 59; VWF:Ac [IU/dL] = 55; FVIII:C [IU/dL] = 57
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.
PreviouslyPublished:
Gene: VWF
Variant: c.4943C>T p.Pro1648Leu
HGVS:
ClinVarID: not found
CAID: CA6402436
gnomAD: 0.000008056 (13 in 1613708) no homozygotes https://gnomad.broadinstitute.org/variant/12-6018475-G-A?dataset=gnomad_r4
17 Type2A (IIE)c.3434G>CN p.Arg1145Pro 26 D3-TIL-3htz Missense B 17 5GPIbR 22
Case: IP #17 (also in row 8 table 6)
DiseaseAssertion: type2A (IIE) VWD
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: HP:0032440 - blood group B
CaseHPOFreeRext: VWF:Ag [IU/dL] = 17; VWF:Ac [IU/dL] = 5; FVIII:C [IU/dL] = 22
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.
PreviouslyPublished:
Gene: VWF
Variant: c.3434G>C p.Arg1145Pro
HGVS:
ClinVarID: not found
CAID: CA383511377
gnomAD: absent
41 Type2A(IIA)c.4718G>TN p.Gly1573Val 28 A2 htz Missense B 56 28 70
Case: IP #41 (also in row 19 table 6)
DiseaseAssertion: type 2A (IIA) VWD
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: HP:0032440 - blood group B
CaseHPOFreeRext: VWF:Ag [IU/dL] = 56; VWF:Ac [IU/dL] = 28; FVIII:C [IU/dL] = 70
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.
PreviouslyPublished:
Gene: VWF
Variant: c.4718G>T p.Gly1573Val
HGVS:
ClinVarID: not found
CAID: CA383499940
gnomAD: absent
11 c.3922C > A p.Arg1308Ser 28 A1 htz Missense O/A 34/77 na/50 64 CSA /82
Case: IP #11 in type 2B VWD sub-cohort
DiseaseAssertion: type 2B VWD
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: HP:0032370 - blood group A
CaseHPOFreeRext: VWF:Ag [IU/dL] = 77; VWF:Ac [IU/dL] = 50; FVIII:C [IU/dL] = 82
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.
PreviouslyPublished:
Gene: VWF
Variant: c.3922C>A p.Arg1308Ser
HGVS:
ClinVarID: not found
CAID: CA383506203
gnomAD: absent
The p.P1127S pathogenic variant lowers von Willebrand factor levels through higher affinity for the macrophagic scavenger receptor LRP1: Clinical phenotype and pathogenic mechanisms
PMID: 35596664
Gene: VWF
HGNCID: 12726
p.Y1349C
Case#: p.Y1349C, Female, Age 29, Caucasian
Disease Assertion: VWD2M
FamilyInfo: 5 affected family members with varied bleeding scores (range 4-14)
Parental Genotype: Not listed
CasePresentingHPOs:
CaseHPOFreeText: bleeding score 8, VWF:Rco/VWF:Ag ratio 0.35, VWF:Rco 17 IU/dL, VWF:Ag 49 IU/dL,
CaseNotHPOs:HP:0040240
(Increased Ratio of VWF Propeptide to VWF antigen)
CaseNotHPOFreeText: normal multimer distribution
Protein Expression:
CasePreviousTesting:VWF Sequencing
Gene: VWF
Variant: NM_000552.4:c.4046A>G (p.Tyr1349Cys)
ClinVar: N/A
CAID: CA383505652
gnomAD: N/A
Intron retention resulting from a silent mutation in the VWF gene that structurally influences the 5′ splice site
PMID: 27543438
Gene: VWF
HGNCID: 12726
Pharmacokinetics, efficacy, and safety of a plasma-derived VWF/FVIII concentrate (VONCENTO) for on-demand and prophylactic treatment in patients with von Willebrand disease (SWIFT-VWD study)
PMID: 27203734
Gene: VWF
HGNCID: 12726
Case#: 01030, Age 12, Female, Blood type:O+ (Table S3)
Disease Assertion: VWD 1
FamilyInfo: Not listed
Parental Genotype: Not listed
CasePresentingHPOs: N/A
CaseHPOFreeText: VWF:Ag: 23, VWF:RCo: 33, FVIII:C: 51, VWF:CB: 33
CaseNotHPOs: N/A
CaseNotHPOFreeText: Bleeding score 2
Protein Expression: N/A
CasePreviousTesting: 48,48 Access-Array amplification. NGS Molecular analysis was performed. Sanger sequencing was used to validate selected mutations.
Gene: VWF
Variant: NM_000552.4:c.2561G>A (p.Arg854Gln)
ClinVar: 296
CAID: CA114139
gnomAD:MAF of 0.005692 (143/25122 alleles) in the European (Finnish) population.
Case#: 30035, Age 55, Female, Blood Type A+ (Table S3)
Disease Assertion: VWD 1
FamilyInfo: The patient is the only member of Family# 3012.
Parental Genotype: Not listed
CasePresentingHPOs: N/A
CaseHPOFreeText: VWF:Ag:25, VWF:RCo:16, FVIII:C:38, VWF:CB: 19
CaseNotHPOs: N/A
CaseNotHPOFreeText: Bleeding Score 1
Protein Expression: N/A
CasePreviousTesting: 48,48 Access-Array amplification. NGS Molecular analysis was performed. Sanger sequencing was used to validate selected mutations.
Gene: VWF
Variant: NM_000552.4:c.5336G>T (p.Arg1779Leu)
ClinVar: N/A
CAID:CA383495656 CAID
gnomAD: MAF of 0.00002891 (1/ 34592 alleles) in the Latino population. gnomAD
Case#: 14003, Age 40, Female, Blood Type O+,
Disease Assertion: VWD 1
FamilyInfo: The patient is the only member of Family#1403.
Parental Genotype: Not listed
CasePresentingHPOs: N/A
CaseHPOFreeText: VWF:Ag:28. VWF:RCo:20,FVIII:C:61, VWF:CB:18
CaseNotHPOs: N/A
CaseNotHPOFreeText: Bleeding Score 6
Protein Expression: N/A
CasePreviousTesting: 48,48 Access-Array amplification. NGS Molecular analysis was performed. Sanger sequencing was used to validate selected mutations
Gene: VWF
Variant: NM_000552.4:c.221-70G>T and NM_000552.4:c.478G>A
ClinVar: N/A
CAID: CA923726380 and CA383518171 CAID1 CAID2
gnomAD: N/A
An association of candidate gene haplotypes and bleeding severity in von Willebrand disease type 2A, 2B, and 2M pedigrees
PMID: 16409463
Notes: several variants, currently curating c.823T>C (p.Cys275Arg) and family 11 proband is compound het with p.Pro1337Leu. Nucleotide position are not provided and the family is asserted as type B but no GPIb, RIPA or VWF platelet binding assay data are reported.
Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study
PMID: 28572165
Gene: VWF
HGNCID: 12726
Feasibility of the Von Willebrand disease PREVENT tria
PMID: 28577390
Gene: VWF
HGNCID: 12726
Dominant Type 1 von Willebrand Disease Caused by Mutated Cysteine Residues in the D3 Domain of von Willebrand Factor
PMID: 8839833 Gene: VWF HGNCID: 12726
Case: Case 1, female, newborn
DiseaseAssertion: VWD2B
FamilyInfo: second child of couple without family history of bleeding, Detection of maternal alloantibodies against HPA antigens present on paternal platelets showed weak cross reactivity, Analysis of platelet genotype for HPA-1, 2, 3, 5, and HPA-15 alleles by PCR-SSP performed in both parents, showed a possible incompatibility in HPA-1b and HPA-5b, No maternal anti-HPA antibody was detected using monoclonal antibody-specific immobilization of platelet antigen method directed against HPA-1, 3, 4, HPA-2, and HPA-5 antigens
ParentalGenotype(s): variant absent in both parents
CasePresentingHPOs: HP:0000967, HP:0001873, HP:0030129
(petechia, thrombocytopenia, impaired ristocetin cofactor assay activity)
CaseHPOFreeText: Delivered at 40wks, VWF:RCo = 8 IU dL−1, VWF:Ag = 105 IU dL−1, VWF:RCo/VWF:Ag < 0.1, FVIII:C = 94 IU dL−1, RIPA not tested due to low platelet count
CaseNOTHPOs: HP:0032169
(infection)
CaseNOTHPOFreeText: DIC, spontaneous bleeding
CasePreviousTesting: NA
GenotypingMethod: sequencing of the whole exon 28 of VWF gene
PreviouslyPublished: NA
Gene: VWF
Variant: c.4379T>C (Leu1460Pro)
HGVS: NM_000552.3:c.4379T>C (Leu1460Pro)
ClinVarID: NA
CAID: CA383502290; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383502290
gnomAD: absent
Screening of female family members of von Willebrand disease patients: utility of a modified screening tool in a high‐risk population
PMID: 28181360
Gene: VWF
HGNCID: 12726
Von Willebrand disease mutation spectrum and associated mutation mechanisms
PMID: 28987708
Gene: VWF
HGNCID: 12726
Type 3 Von Willebrand Disease: A Case Report of a Rare Entity
Gene: VWF
HGNCID: 12726
Case: 4 month old female
DiseaseAssertion: VWD type 3
FamilyInfo: both parents were sequenced ParentalGenotype(s): mother is VWF:c.2435delC carrier, father was negative
CasePresentingHPOs: HP:0011889 CaseHPOFreeRext: bleeding from injection site following vaccination administration CaseNOTHPOs: CaseNOTHPOFreeText: normal PT/PTT at 4 months. prolonged PTT, normal PT and platelet count upon repeat. Factor VIII levels <1%, VWF activity <15%
GenotypingMethod: unknown
Gene: VWF
Variant: c.2435delC in VWF gene, deletion in exon 6 of VWF gene
HGVS: NM_000552.5:c.2435del
ClinVarID: 303
gnomAD: 0.00007187 (116/1613916) https://gnomad.broadinstitute.org/variant/12-6044297-CG-C?dataset=gnomad_r4
Alloantibodies in von Willebrand disease
PMID: 29165738
Gene: VWF
HGNC: 12726 (type 1)
Note: Insufficient Evidence due to lack of variant information. This paper designates variants as only "missense, deletion, etc" and lacks specific neucleotide changes. All probands with identifiable variants in this paper were from other PMIDs, which were confirmed to be previously curated or added to the list to be curated.
c.4136 G>T
Gene:VWF
HGNCID:12726
PMID33550910
Case:38-year-old woman from Saudi Arabia
DiseaseAssertion:VWD type 2B
FamilyInfo:Mother and brother suffered from epistaxis (no genotypes). Two sons and one daughter: both sons carry the same mutation, but only one presents with minimal epistaxis.
ParentalGenotype(s):Not available
CasePresentingHPOs:HP:0001934, HP:0004846, HP:0011871
CaseNOTHPOs:HP:0000421, HP:0000132
CaseNOTHPOFreeText:multiple dental extractions without bleeding complications
CaseHPOFreeRext:RIPA (+) Rist 0.5 mg/mL
CasePreviousTesting:No
GenotypingMethod:NGS
Gene:VWF
Variant:c.4136 G>T (p. R1379 L)
HGVS:NC_000012.12:g.6019282C>A
ClinVarID:
CAID:CA383504438
gnomAD: