Case#: Patient 89, Turkey

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguineous parents

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.826_828del (p.Glu276del)

Variant1ClinVarID: 2734638

Variant1CAID: CA2586965949

Variant2: c.826_828del (p.Glu276del)

Variant2ClinVarID: 2734638

Variant2CAID: CA2586965949

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, Italy

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.1487C>G (p.P496R)

Variant1ClinVarID: 496861

Variant1CAID: CA2802275

Variant2: c.793G>C (p.G265R)

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 11, Italy

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.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.532G>A (p.E178K)

Variant2ClinVarID: 2203495

Variant2CAID: CA355961709

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 30, 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

Case#: Patient 79, Turkey

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.1727+6T>A

Variant1ClinVarID: 2203499

Variant1CAID: CA2580070698

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 21394825

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 13, Italy

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.265C>T (p.R89W)

Variant1ClinVarID: 580286

Variant1CAID: CA2801156

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 19, 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.1727+1G>A

Variant1ClinVarID: 638077

Variant1CAID: CA355965296

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 33, 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

Case#: Patient 29, 1 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding (HP:0000280, HP:0001433, HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.6% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1339delC (p.Arg447Alafs*10)

Variant1ClinVarID: N/A

Variant1CAID: CA2586965980

Variant2: c.1339delC (p.Arg447Alafs*10)

Variant2ClinVarID: N/A

Variant2CAID: CA2586965980

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 35, 3 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: 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.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

Case#: Patient 57, 6 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0100790)

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.895G>T (p.Glu200Ter)

Variant1ClinVarID: 987878

Variant1CAID: CA355962511

Variant2: c.1960T>A (p.Ter654Arg)

Variant2ClinVarID: N/A

Variant2CAID: CA355966128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 45, 10 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, joint contractures, corneal clouding, recurrent infections, intellectual disability (HP:0000280, HP:0002828, HP:0007957, HP:0002719, HP:0001249)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.0% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1898C>T (p.Ser633Leu)

Variant1ClinVarID: 556406

Variant1CAID: CA355966010

Variant2: c.1898C>T (p.Ser633Leu)

Variant2ClinVarID: 556406

Variant2CAID: CA355966010

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 32, 3 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: Sibling of Patient 31

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: 2.5% (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

Case#: Patient 20, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, intellectual disability (HP:0000280, HP:0001433, HP:0001249)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 4.0% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.793-1G>A

Variant1ClinVarID: 557472

Variant1CAID: CA2802097

Variant2: c.793-1G>A

Variant2ClinVarID: 557472

Variant2CAID: CA2802097

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 9, 11 years old (age at report), female, 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: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 4.5% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.523_534del (p.Trp175_Glu178del)

Variant1ClinVarID: 2734635

Variant1CAID: CA645372297

Variant2: c.523_534del (p.Trp175_Glu178del)

Variant2ClinVarID: 2734635

Variant2CAID: CA645372297

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 24, 1 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, joint contractures, corneal clouding, dysostosis multiplex, intellectual disability (HP:0000280, HP:0002828, HP:0007957, HP:0000943, HP:0001249)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1096_1099del (p.Thr366Argfs*73)

Variant1ClinVarID: 1065522

Variant1CAID: CA2499217017

Variant2: c.1096_1099del (p.Thr366Argfs*73)

Variant2ClinVarID: 1065522

Variant2CAID: CA2499217017

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: P2 8yrs male, age at initial diagnosis 5 yrs, age at definitive diagnosis 8 yrs DiseaseAssertion: mucopolysacchari- dosis type I (MPS I FamilyInfo:Nil CasePresentingHPOs: HP:0012185 (Constrictive median neuropathy) HP:0001376 (Limitation of joint mobility ) HP:0001387 (Joint stiffness) CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: IDUA activity: undetectable CaseUrineGAGs: Chondroitin sulfate (urine): 5.4 mg/mmol creat. Dermatan sulfate (urine): 5.5 mg/mmol creat. Heparan sulfate (urine): 37 mg/mmol creat. Keratan sulfate (urine): 7.4 mg/mmol creat. Normal values : chondroitin sulfate: 6.1 ± 3.4 mg/mmol creat.; dermatan sulfate: 2.4 ± 0.7 mg/mmol creat.; heparan sulfate: 9.4 ± 5.3 mg/mmol creat.; keratan sulfate: 12.9 ± 7.6 mg/mmol creat.; CaseERT: Don't know

CaseBMT: Don't know Variant1: IDUA:c.1524+2T>A, NM_000203.5; Transcriptomic analysis confirmed an insertion of four nucleotides between exons 10 and 11 in IDUA due to the disruption of the cryptic donor splicing site of exon 10. Variant1ClinVarID: Variant1CAID: CA355964832 Variant2: IDUA:c.-87T>C, NM_000203.5; Gene Expression Analysis by Luciferase Reporter Assay - 87% reduction was recorded in the context of the mutant IDUA promoter compared to the wild-type promoter. Variant2ClinVarID: Variant2CAID: CA2586973509 AdditionalVariants: ParentalGenotype: c.1524+2T>A (paternal) c.-87T>C (maternal) PreviouslyPublished No

Case#: Patient 1 was biochemically diagnosed with MPS I because they showed an increase in urinary GAGs and a reduction in IDUA activity in leukocytes. Patient 1 was diagnosed at 2 years and 3 months.

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facies, corneal clouding, intellectual disability, skeletal abnormalities, cardiac abnormalities, and hepatosplenomegaly (HP:0000256, HP:0007957, HP:0001249, HP:0002360, HP:0001627, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: Growth delay, hernias (HP:0001510, HP:0100790)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity of 1.92 nmol/mg/protein/hr. No reference range provided.

CaseUrineGAGs: 1115.4 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.683delC (p.P228Hfs*6)

Variant2ClinVarID: N/A

Variant2CAID: CA2580610937

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7 was biochemically diagnosed with MPS I because they showed an increase in urinary GAGs and a reduction in IDUA activity in leukocytes. Patient 7 was diagnosed at 2 years and 11 months.

DiseaseAssertion: MPSI-S

FamilyInfo: N/A

CasePresentingHPOs: Coarse facies, corneal clouding, skeletal abnormalities, cardiac abnormalities, and hepatosplenomegaly (HP:0000256, HP:0007957, HP:0002360, HP:0001627, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: Growth delay, hernias, intellectual disability (HP:0001510, HP:0100790, HP:0001249)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity of 2.35 nmol/mg/protein/hr. No reference range provided.

CaseUrineGAGs: 1011.7 CPC unit/g creatinine. No reference range provided.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1037T>G (p.L346R)

Variant2ClinVarID: 11927

Variant2CAID: CA256128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2 was biochemically diagnosed with MPS I because they showed an increase in urinary GAGs and a reduction in IDUA activity in leukocytes. Patient 2 was diagnosed at 1 year.

DiseaseAssertion: MPSI-H/S

FamilyInfo: N/A

CasePresentingHPOs: Coarse facies, corneal clouding, skeletal abnormalities, cardiac abnormalities, and hepatosplenomegaly (HP:0000256, HP:0007957, HP:0002360, HP:0001627, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: Intellectual disability, growth delay, hernias (HP:0001249, HP:0001510, HP:0100790)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity of 2.8 nmol/mg/protein/hr. No reference range provided.

CaseUrineGAGs: 733.8 CPC unit/g creatinine. No reference range provided.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1163C>A (p.T388K)

Variant1ClinVarID: 198696

Variant1CAID: CA247499

Variant2: c.1163C>A (p.T388K)

Variant2ClinVarID: 198696

Variant2CAID: CA247499

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, male, 11 months (age of onset), 2 years (age at report)

DiseaseAssertion: MPS1

FamilyInfo: Born from a second-degree consanguineous marriage, has a healthy older brother.

CasePresentingHPOs: Claw hand deformity, extended Mongolian blue spot, hernia, macrocephaly, neurodevelopmental delay, dysostosis multiplex (HP:0034337, HP:0011369, HP:0100790, HP:0000256, HP:0012758, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: Intellectual disability (HP:0001249)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Low level of IDUA enzyme activity

CaseUrineGAGs: Negative GAG-excretion

CaseERT: N/A

CaseBMT: N/A

Variant1: c.523T>C (p.W175R)

Variant1ClinVarID: 226412

Variant1CAID: CA10576337

Variant2: c.523T>C (p.W175R)

Variant2ClinVarID: 226412

Variant2CAID: CA10576337

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2, female, 2 years (age of onset), 5 years (age at report)

DiseaseAssertion: MPS1

FamilyInfo: Born from a consanguineous marriage (second cousin parents), she had a twin sister that died a few weeks after birth. Her mother experienced intrauterine fetal death (IUFD) during her first pregnancy and after the second pregnancy infant died of congenital heart defects (CHD).

CasePresentingHPOs: Claw hand deformity, deafness, coarse facial features, dolichocephaly, neurodevelopmental delay, developmental regression (HP:0034337, HP:0000365, HP:0000256, HP:0000268, HP:0012758, HP:0002376)

CaseHPOFreeText: Began pronouncing words at 9 months, sitting at 10 months, and started walking at the age of 2. Her developmental conditions lapsed after the age of 2.

CaseNotHPOs: Intellectual disability (HP:0001249)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: GAG electrophoresis revealed increased amounts of DS and CS

CaseERT: She currently is taking Aldorazyme medication

CaseBMT: N/A

Variant1: c.612_615dupCTGC

Variant1ClinVarID: 226413

Variant1CAID: CA10576338

Variant2: c.612_615dupCTGC

Variant2ClinVarID: 226413

Variant2CAID: CA1057633

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 3 (19 y, male - cousin of Cases 1 and 2, symptom onset/pain+movement limittion 12y, diagnosis 19y))

DiseaseAssertion: Scheie syndrome

FamilyInfo: Male patient born to consanguineous parents

CasePresentingHPOs:

CaseHPOFreeText: electroneurology showed bilateral signs of mild median nerve suffering.

CaseNotHPOs: 0034337;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: 0.57 (umol/g/h)

CaseUrineGAGs:

CaseERT: Yes, after diagnosis at 19y

CaseBMT:

Variant1:c.1189+4A>T

Variant1ClinVarID:

Variant1CAID: CA2586965965

Variant2: 1189+4A>T

Variant2ClinVarID:

Variant2CAID: CA2586965965

AdditionalVariants:

ParentalGenotype:

PreviouslyPublished

Case#: Patient 6, male, Han origin, 13 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Macrocephaly (HP:0000256)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

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.589G>A (p.G197S)

Variant2ClinVarID: 1526094

Variant2CAID: CA355961839

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#: Patient 16, male, Han origin, 2.5 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

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: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Cardiac disease

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.2T>C (p.M1?)

Variant1ClinVarID: 639529

Variant1CAID: CA2801095

Variant2: c.1593delG (p.Leu532CysfsTer28)

Variant2ClinVarID: N/A

Variant2CAID: CA2586965986

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#: Patient 23, male, Han origin, 3.5 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: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 3.5 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.1-2C>G

Variant1ClinVarID: N/A

Variant1CAID: CA2586973510

Variant2: c.1189+5G>T

Variant2ClinVarID: N/A

Variant2CAID: CA2586965966

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#: Patient 2, Han origin, male, 1 year and 3 months old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Airway obstruction (HP:0006536)

CaseNotHPOFreeText: N/A

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.159C>A (p.C53X)

Variant1ClinVarID: 1458768

Variant1CAID: CA355945972

Variant2: c.546G>C (p.E182D)

Variant2ClinVarID: 4069690

Variant2CAID: CA355961740

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#: Patient 29, male, Han origin, 11 years old (age at diagnosis)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Macrocephaly, Joint stiffness, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0000256, HP:0001387, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay, Mongolian macula (HP:0001263, HP:0011369)

CaseNotHPOFreeText: N/A

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.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

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#: Patient 35, female, Han origin, 3 years old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: Mongolian macula (HP:0011369)

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.1227dupG (paper says c.1225dupC but according to the variant sequence this should be c.1227dupG - a known variant)

Variant1ClinVarID: 929237

Variant1CAID: CA1139658406

Variant2: c.1244_1271del27 - Allele registry states that the range is off by 1, noting a deletion of 28 being found instead of 27.

Variant2ClinVarID: N/A

Variant2CAID: N/A

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#: 51 year old patient, Italy, male

DiseaseAssertion: MPS1-H/S

FamilyInfo: This patient also had an affected MPS1-H/S sibling. Their mother was not only an MPS1 carrier but also had Fabry disease.

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.1189+5G>A

Variant1ClinVarID: 551848

Variant1CAID: CA658823290

Variant2: c.46_57del (p.Ser16_Ala19del)

Variant2ClinVarID: 92643

Variant2CAID: CA220509

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished Yes - PMID: 21394825

Case#: Infant #2, male.

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 1.50 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 34.02, DS - 0.11, HS - 0.17, KS - 0.53 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.1395delC (p.G466AfsTer59)

Variant1ClinVarID: 929236

Variant1CAID: CA549264595

Variant2: c.1081G>A (p.A361T)

Variant2ClinVarID: 92624

Variant2CAID: CA145865

AdditionalVariants: c.1816G>T (p.V606L), ClinVarID: 2432754, CAID: CA2802416

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#:4. 1.5 year Male, diagnosed at 1.3 years DiseaseAssertion:MPS1H FamilyInfo:NA CasePresentingHPOs:NA CaseHPOFreeText:NA CaseNotHPOs:NA CaseNotHPOFreeText:NA CaseEnzymeAssay:Undetectable CaseUrineGAGs:NA CaseERT:NA CaseBMT:Yes, matched sibling donor, Post HSCT 13.24 nmol/h/mg of protein ( α-l-Iduronidase Levels) Variant1:IDUA : c.1598C>G Variant1ClinVarID:11910 Variant1CAID: CA256112 Variant2:IDUA: c.1205G>A Variant2ClinVarID: 11908 Variant2CAID:CA220498 AdditionalVariants: ParentalGenotype: PreviouslyPublished

Case#: Patient 37 (Table 3)

DiseaseAssertion: Severe MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 13 nmol/h/mg per DBS (dried blood spots) determined during NBS. 21.1 DBS protein concentration determined by Immuno-SRM (pmol/L).

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Yes

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: IV-2, Male, Yemeni, deceased at age 5 years

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Parents are consanguineous first cousins (Pedigree figure #1)

CasePresentingHPOs: HP:0001640, HP:0000280, HP:0002516 (Cardiomegaly, Coarse Facial Features, Intracranial hypertension)

CaseHPOFreeText: Dysplasia

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: Both parents are heterozygous for the c.657delA variant of the gene (see pedigree @ figure#1)

PreviouslyPublished N/A

PMID: 24314423 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive

Case#:Patient Sample unique ID 29, 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 0.623 (7.5) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 11.1 pmol/punch/h Confirmatory IDUA enzyme

CaseUrineGAGs: DS 3.1 g/mol creatinine and HS 2.4 g/mol creatinine (Normal)

CaseERT:No

CaseBMT:No

Variant1:heterozygous VUS: c.787A>T; p.R263W (Normal examination)

Variant1ClinVarID:2664494

Variant1CAID:CA411263334

Variant2: heterozygous PD: c.246C>G; p.H82Q

Variant2ClinVarID:92637

Variant2CAID:CA220506

AdditionalVariants:None

ParentalGenotype:None provided

PreviouslyPublished:N/A

PMID: 36541357

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1877G>A (p.W626X)

Variant2ClinVarID: 928997

Variant2CAID: CA355965968

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.501C>G (p.Y167X)

Variant2ClinVarID: 92644

Variant2CAID: CA220511

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Male, first evaluated at 3.5 years, diagnostic studies described in paper at age 4.5 years, at time of report 11 years

DiseaseAssertion: Mucopolysaccharidosis Type I and Type II

FamilyInfo:Clinically normal sister, mother and father; parents denied consanguinity; extensive histocompatibility typing of all family members confirmed relationships and did not suggest consanguinity; Maternal uncle died at 11 years having "coarse facial features" but not diagnostic testing. Pedigree, Figure 7, page 82.

CasePresentingHPOs: HP:0000943 (dysostosis multiplex); HP:0000280 (course facial features)

CaseHPOFreeText: at 3.5 years "...gross motor delay, mild expressive language delay, and progressive changes in facial features and joints...noted to be a noisy breather and have a history of frequent ear infections...prominent metopic suture and facial features were said to be coarsened" Height 50th%, weight 95th%, head circumference >98th%. At 11 years of age reported to show progressive intellectual deterioration.

CaseNotHPOs:

CaseEnzymeAssay: Table 2 (page 79): leukocyte IDUA (alpha-L) activity absent (<1.0 nmol/mg/h), plasma IDUA alpha-L <0.20 MU/ml/h); plasma IDS activity was undetectable (0.0 U/mg/h)

CaseUrineAssay:Not reported

CaseERT:Don't know

CaseBMT:Don't know

Variant1:IDUA W402X

Variant1ClinVarID:11908

Variant1CAID:

Variant2: IDUA A300T

Variant2ClinVarID: 11923

Variant2CAID:

AdditionalVariants: IDS R468W (missense 1402C-->T), ClinVarID: 10497

ParentalGenoype:Mother, IDUA A300T and IDS R468W; Father, IDUA W402X

PreviouslyPublished:

Case#: Patient 2 (see Table 1), 1 year and 3 months - deceased (age at report), 1 month and a half (age at onset), male, height of 71 cm, weight of 12 kg, located in the Sfax: Industrial region.

DiseaseAssertion: MPS1 - severe

FamilyInfo: Two affected siblings (Patients 1 and Patient 3), three other familial relations (deceased), parents were 3rd cousins (see Table 2) aged 38 yrs (M) and 40 yrs (F).

CasePresentingHPOs: HP:0000280, HP:0002194, HP:0000238, HP:0000365, HP:0000023 (Coarse facial features, developmental delay, hydrocephaly, hearing impairment, inguinal hernia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: (p.F602X)

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: (p.F602X)

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: P1-IDUA, F Europeanin Italy DiseaseAssertion: MPS 1: Psuedo/Hurler FamilyInfo: CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: NBS 1.36 triplex/3.4 single CaseUrineGAGs: CaseERT: CaseBMT: Variant1: c.246C > G Variant1ClinVarID: 92637 Variant1CAID: CA220506 Variant2: c.1205G > A Variant2ClinVarID: 11908 Variant2CAID: CA220498 AdditionalVariants: ParentalGenotype: PreviouslyPublished

PMID: 30442156 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive

Case#: Patient 27 (see Table 2), Gestational age unavailable

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 1.70 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA:234128

Variant2: c.1148G>A (p.R383H)

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 12 (see Table 2), 40 weeks (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: 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

Case#: Patient 23, male, 2 years (age at presentation).

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family not present for this patient. There was a prenatal diagnosis "CVS-carrier for p.M504R"

CasePresentingHPOs: Corneal clouding, coarse facial features, dystosis multiplex, hepatomegaly, joint stiffness, motor delay, splenomegaly, short stature (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0001387, HP:0001270, HP:0001744, HP:0004322)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1511T>G (p.M504R)

Variant1ClinVarID: N/A

Variant1CAID: CA355964770

Variant2: c.1524+1G>C

Variant2ClinVarID: 3653693

Variant2CAID: CA355964828

AdditionalVariants: N/A

ParentalGenotype: Father is a carrier for p.M504R and mother is a carrier for c.1524+1G>C

PreviouslyPublished N/A

Case#: Patient 2, female, 6 years (age at presentation)

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, dysostosis multiplex, hepatomegaly, joint contractures, splenomegaly (HP:0007957, HP:0000943, HP:0002240, HP:0100790, 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.223G>C (p.A75P)

Variant1ClinVarID: N/A

Variant1CAID: CA355946364

Variant2: c.223G>C (p.A75P)

Variant2ClinVarID: N/A

Variant2CAID: CA355946364

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 27, female, 1 year 6 months (age at presentation).

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, dysostosis multiplex, hepatomegaly, inguinal hernia, joint stiffness, sleep disturbances, splenomegaly, umbilical hernia (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0000023, HP:0001387, HP:0002360, HP:0001744, HP:0001537)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1855C>T (p.R619X)

Variant1ClinVarID: 280976

Variant1CAID: CA2802455

Variant2: c.1855C>T (p.R619X)

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 18, born in 2012 (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: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 79.39 ng/mol (42.66 weight matched enzyme reference assay)

CaseUrineGAGs: 0.51 DS/CS

CaseERT: Yes

CaseBMT: Yes, Uncle

Variant1: c.1045G>T (p.D349Y)

Variant1ClinVarID: 638075

Variant1CAID: CA355963146

Variant2: c.1045G>T (p.D349Y)

Variant2ClinVarID: 638075

Variant2CAID: CA355963146

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 20, born in 2003 (paper published in 2017), 20 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: 57.2 ng/mol (26 weight matched enzyme reference assay)

CaseUrineGAGs: 0.63 DS/CS

CaseERT: No

CaseBMT: Yes, Cord

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1898C>A (p.S633X)

Variant2ClinVarID: 1068474

Variant2CAID: CA355966009

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 12, Female, 0.9 years (diagnosed), 10.1 years (report), 26 kg (weight), 108 cm (height), Iranian

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs: HP:0001999, HP:0100790 (Facial Dysmorphic Features, Hernia)

CaseHPOFreeText: HM/HSM

CaseNotHPOs: HP:0001249, HP:0000943, HP:0001387, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Multiple Dysostosis, Joint Stiffness, Deafness, Corneal Opacity, Hydrocephalus)

CaseNotHPOFreeText: Chronic Rhinorrhea, Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 1.01 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 7.4 (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

Case#: 2, Male, 0.9 years (diagnosed), 4.2 years (report), 11 kg (weight), 65 cm (height), Iranian

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs: HP:0000943, HP:0001387 (Multiple Dysostosis, Joint Stiffness)

CaseHPOFreeText: HM/HSM,

CaseNotHPOs: HP:0001249, HP:0001999, HP:0100790, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Hernia, Deafness, Corneal Opacity, Hydrocephalus)

CaseNotHPOFreeText: NM/HSM, Chronic Rhinorrhea, Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 7.06 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 14.22 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.S157P

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Functional assay variant with a clinical significance of having conflicting interpretations.

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.1577T>C (p.L526P)

Variant1ClinVarID: 567566

Variant1CAID: CA2802300

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of being a VUS.

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.904C>A (p.P302T)

Variant1ClinVarID: 1067236

Variant1CAID: CA355962529

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of being a VUS.

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.787A>T (p.R263W)

Variant1ClinVarID: 550605

Variant1CAID: CA2802085

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of being a VUS.

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.1757C>T (p.S586P)

Variant1ClinVarID: 571910

Variant1CAID: CA2802396

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

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: L346R

Variant1ClinVarID: 11927

Variant1CAID: CA256128

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: F188L

Variant1ClinVarID:

Variant1CAID: CA355961777

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: W306L

Variant1ClinVarID: 2203497

Variant1CAID: CA355962596

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: P533R

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: PKMPS1P11, 8 years old (age at presentation), female, Pakastani. Poor performance in school due to difficulty in writing.

DiseaseAssertion: MPS-I

FamilyInfo: Born to parents in a consanguineous marriage

CasePresentingHPOs: Coarse facial features, joint stiffness, stunted and mild thoracic kyphosis (HP:0000256, HP:0001387, HP:0002808)

CaseHPOFreeText: Widening of the wrist

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

Case#:Patient Sample unique ID 2

DiseaseAssertion:MPS type I-Hurler children

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:Obstructive sleep apnea, HP:0002870

CaseNotHPOFreeText:None

CaseEnzymeAssay:None

CaseUrineGAGs: Tested but amounts not reported

CaseERT:No

CaseBMT:Hematopoietic stem cell transplantation

Variant1: c.979G>C

Variant1ClinVarID:167190

Variant1CAID:CA234128

Variant2:None

Variant2ClinVarID:None

Variant2CAID:None

AdditionalVariants:None

ParentalGenotype:None provided

PreviouslyPublished:N/A

PMID:20553232

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: OS of sibship 9, female, 7 years old (age at diagnosis), 14 years old (age at ERT enrollment), 7 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Affected YS (YS of sibship 9)

CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contracture)

CaseHPOFreeText: Cardiac disease, ocular, respiratory, and musculoskeletal involvement.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - At T2, ocular and cardiac symptoms progressed from mild to moderate/severe. In addition, pulmonary function worsened, and contractures and lower extremity weakness progressed. Had stabilization of dysostosis multiplex and no progression of motor function delays.

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#: Case information was not provided

DiseaseAssertion: MPS I-H/S

FamilyInfo: Proband of family B

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.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: c.1469T>C (p.L490P), Confirmed homozygous in Figure 1

Variant2ClinVarID: 11919

Variant2CAID: CA220503

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 17, Cyprus

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.659delG; c.747delG in the paper (old nomenclature)

Variant1ClinVarID: N/A

Variant1CAID: CA2802045

Variant2: c.659delG; c.747delG in the paper (old nomenclature)

Variant2ClinVarID: N/A

Variant2CAID: CA2802045

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 20, UK

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.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.65delC; c.153delC in the paper (old nomenclature)

Variant2ClinVarID: 929238

Variant2CAID: CA437911597

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 5 (Thai, male, diagnosed age 7y)

DiseaseAssertion: MPS1

FamilyInfo: Thai, no consanguinity

CasePresentingHPOs: 0007759 (cloudy cornea); 0034337 (claw hand): 0002240 (hepatomegaly); 0001387 (multiple joint stiffness); 0000280 (coarse facies); 0000365 (hearing impairment)

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: no neurological symptoms detected

CaseEnzymeAssay: 3.27 nmole/18 h/mg protein

CaseUrineGAGs:

CaseERT:

CaseBMT:

Variant1:IDUA c.1138C>T (p.Q380X)

Variant1ClinVarID:

Variant1CAID:

Variant2: IDUA c.*1T>C Ex14 (p.X654Rext38)

Variant2ClinVarID:

Variant2CAID:

AdditionalVariants:

ParentalGenotype:

PreviouslyPublished

Case#: 4 (Thai, female, diagnosed at 4y6m)

DiseaseAssertion: MPS1

FamilyInfo: Thai, no consanguinity

CasePresentingHPOs: 0007759 (cloudy cornea); 0002240 (hepatomegaly); 0002857 (knock knee)

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: no neurological symptoms detected

CaseEnzymeAssay: 3.23 nmole/18 h/mg protein

CaseUrineGAGs:

CaseERT:

CaseBMT:

Variant1:IDUA c.935G>A: Ex7 (p.W312X)

Variant1ClinVarID: 8555322

Variant1CAID:

Variant2: IDUA c.*1T>C Ex14 (p.X654Rext38)

Variant2ClinVarID:

Variant2CAID:

AdditionalVariants:

ParentalGenotype:

PreviouslyPublished

Case#: male, 23 year olds (age at report), progressive impairment in ability to perform in school.

DiseaseAssertion: MPS I-H/S

FamilyInfo: N/A

CasePresentingHPOs: Mental deterioration (HP:0001268)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - the patient had been treated with intravenous rhIDU for 13 years before IT rhIDU and had not undergone HSCT. The patient was also enrolled concurrently in an IRB approved non‐interventional longitudinal study of brain structure and function in MPS at the University of Minnesota. He showed stable or improved neurocognitive outcomes after 24 months of IT rhIDU. The patient showed the greatest improvement in his ability to encode verbal stimuli, moving from significantly impaired to the average level. This was accompanied by a significant improvement in adaptive behavior and an improvement to an above average level, in his ability to remember verbal material in a context. Nonverbal memory, both encoding and recall increased although those scores remained below the average range. A baseline of average IQ and attention performance also somewhat improved.

CaseBMT: No

Variant1: c.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA234128

Variant2: c.793G>C (p.G265R)

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 8 year-old Chinese Han boy. At age 3 years physical disabilities began appearing.

DiseaseAssertion: Mucopolysaccharidosis type I, MPS-I

FamilyInfo: Proband is the third child of healthy non-consanguineous parents. Paper states there is "no family history of related genetic diseases." Figure 1 has a pedigree of proband's family.

CasePresentingHPOs: HP:0000280 (coarse facial features), HP:0000256 (macrocephaly), HP:0007957 (corneal clouding), HP:0000158 (macroglossia), HP:0004322 (short stature), HP:0000470 (short neck), HP:0001537 (umbilical hernia), HP:0034392 (joint contracture), HP:0011369 (large Mongolian spot on the back skin), HP:0040079 (irregular teeth), HP:0002240 (hepatomegaly), HP:0034337 (claw hand deformity),

CaseHPOFreeText: Dorsal kyphosis; extreme myopia found via optical examination (visual acuity reached 0.4 in right eye and 0.5 in left eye); thickening of heart valves, mild tricuspid, and aortic valve regurgitation found via Color Doppler ultrasonography; normal intelligence indicated with Wechsler Preschool and Primary Scale of Intelligence scale; cone-shaped phalanges; bilateral coxa vara; small epiphyses on the distal femur and proximal-distal tibiofibula; thin bone cortex; short femoral shaft; multiple diffuse abnormal signals in the bilateral frontal-parietal lobes and left part of the corpus callosum; proband was born at a 3.35 kg weight and 51 cm height

CaseNotHPOs:

CaseNotHPOFreeText: No prominent abnormalities found in blood thyroid hormone levels

CaseEnzymeAssay: "alpha-L-iduronidase activity was significantly decreased in the patient leukocytes (0.65 nmol/h/mg protein)"

CaseUrineGAGs: No urine GAG levels reported for this proband

CaseERT: Don't know

CaseBMT: Don't know

Variant1: c.159‐9T>A

Variant1ClinVarID:

Variant1CAID: CA3044589050

Variant2: c.159‐9T>A

Variant2ClinVarID:

Variant2CAID: CA3044589050

AdditionalVariants: No other pathogenic variants were found/were associated with clinical features

ParentalGenotype: Proband's father is heterozygous for c.159‐9T>A IDUA mutation. DNA from mother and sister of proband showed wild-type allele. Paper states that proband's MPS-I is "caused by UPD(4)pat leading to homozygosity for one pathogenic splicing variant. . ."

PreviouslyPublished: No mention of previous publication

Case#: Subject 4, male in his 10s (age at enrollment), died in his sleep within the first 48 hours of the initial dose during pilot study.

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0002176, HP:0001638 (Spinal cord compression, cardiomyopathy)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Enzyme replacement therapy with laronidase

CaseBMT: N/A

Variant1: c.1208G>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

Case#: 15, Female, Infancy (onset), 10 months (diagnosed), 12 years (report)

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0004322, HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0000023, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Macrocephaly, Joint Stiffness, Hepatomegaly (moderate), Splenomegaly (moderate), Inguinal Hernia, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (Delayed), Systolic murmur 3-4/6, After ERT: decreased illness (obstructive bronchitis), decreased organomegaly, increased mobility)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: Decreased excretion of GAGs in the urine

CaseERT: Had an ERT

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.R628X

Variant2ClinVarID: 550421

Variant2CAID: CA2802462

AdditionalVariants: p.A8, p.A20, p.Q33H, p.L118

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 3, Female, 6 months (onset), 13 months (diagnosed), 14 months (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0002240, HP:0001744, HP:0000280, HP:0000943, HP:0007957 (Hepatomegaly (moderate), Splenomegaly (mild), Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Developmental quotient 92 in 13m), Hyperechogenic mitral valve (with insufficiency of 1st-2nd grade)

CaseNotHPOs: HP:0004322, HP:0000256, HP:0001387 (Short Stature, Macrocephaly, Joint Stiffness)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation (performed in March 2008)

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: p.W402X

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 10, Male, 2 months (onset), 2 months (diagnosed), 2 months (report), deceased (due to severe graft versus host disease)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0002240, HP:0001744, HP:0001537, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Hepatomegaly (moderate), Splenomegaly (moderate), Umbilical Hernia, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Delayed since early infancy)

CaseNotHPOs: HP:0000256 (Macrocephaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation at 5m

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.Q70X

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: p.Q33H/Q33H, p.L118/L118

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#:Table II, MPS-1, Enzyme activity=1.05

DiseaseAssertion: MPS1

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: 1.05 umol/hr/L blood, newborn blood spot

CaseUrineGAGs:

CaseERT:

CaseBMT:

Variant1:c.208C>T (p.Gln70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.208C>T (p.Gln70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants:

ParentalGenotype:

PreviouslyPublished

PMID: 31298590

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 4, 11 years old, Iranian

DiseaseAssertion: MPS1-H (Severe)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity not detected

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1029C>A (p.Y343X)

Variant1ClinVarID: 222997

Variant1CAID: CA356984

Variant2: c.1029C>A (p.Y343X)

Variant2ClinVarID: 222997

Variant2CAID: CA356984

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8, male, 5 months (age at HSCT), 0.9 months (age at ERT)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Veno-occlusive disease (VOD), adenovirus infection

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.06 (at diagnosis), 20.1 (after HSCT) Units not provided.

CaseUrineGAGs: N/A

CaseERT: Yes - 124 days duration

CaseBMT: Yes - Through a sibling with stem cells sourcing from the BM (bone marrow).

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

Case#: Patient 9, female, 7.9 months (age at diagnosis), 12.0 months (age at HSCT), 9.5 - 12.7 months (age at ERT), 4 MRI + neuropsychological observations over the course of 7 years.

DiseaseAssertion: MPS-1H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 24.8 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.1487C>G (p.P496R)

Variant1ClinVarID: 496861

Variant1CAID: CA2802275

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

1 individual from "other regions" was reported to have this variant in a cohort of 291 people with MPS1.

CAID: CA355961907

Genotype: NM_000203.3 c.606C>A p.(Tyr202Ter)

HPOFreeText: Phenotype: unknown

GenotypingMethod: bidirectional Sanger sequencing of the IDUA gene. IDUA exons and adjacent intron regions were amplified by PCR reactions and then sequenced

SupplementalInfo: Supplemental table S1

Mentioned that this variant has been seen in a previous publication: Matte (2003), but it doesn't sound like it's the same individual

Case#: No additional case information provided

DiseaseAssertion: MPSI-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.4 umol/g hr, reference range 10–50 umol/g hr.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1871A>T (p.D624V)

Variant1ClinVarID: N/A

Variant1CAID: CA355965955

Variant2: c.17_24dupCCCGCGCC (p.A9PfsTer102)

Variant2ClinVarID: N/A

Variant2CAID: CA645372294

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/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: 0.09 umol/g hr, reference range 10–50 umol/g hr.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1278_1284dupCCCCCAG (p.G429PfsTer82)

Variant1ClinVarID: N/A

Variant1CAID: CA645372299

Variant2: c.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Pt 5, age is 11 months (proband can be found in Table 1)

DiseaseAssertion: Hurler syndrome, mucopolysaccharidosis type IH, MPS IH, MPS type I

FamilyInfo: No family information provided

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: In methods it is stated that an IDUA activity assay was conducted on cartilaginous pellets generated from patient-derived bone marrow stromal cells at 5 weeks. However, results of the IDUA activity assays are not stated.

CaseUrineGAGs: "Significantly higher levels of GAGs in MPS IH compared with HD pellets at.1 week of chondrogenic differentiation, thus indicating that GAG accumulation in MPS IH can be seen during cell condensation and early differentiation stages." Total GAG content for each sample in ug GAG/ug DNA shown in Figure 4 graphs.

CaseERT: Don't know

CaseBMT: Don't know

Variant1: p.W402X

Variant1ClinVarID:

Variant1CAID: PA3051368272

Variant2: p.W402X

Variant2ClinVarID:

Variant2CAID: PA3051368272

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental information provided

PreviouslyPublished: No mention of being previously published