Genetic Analysis of RAB39B in an Early-Onset Parkinson's Disease Cohort
PMID: 32670181
Gene: RAB39B
Disease: early-onset parkinsonism-intellectual disability syndrome
MonDO: MONDO:0010709
Notes: The report analyzed RAB39B variation in a cohort of 176 individuals with early-onset Parkinson disease by copy number variation analysis, 5' and 3' UTR analyses. However, variants identified were classified as likely benign or uncertain significance.
Increased Dosage of RAB39B Affects Neuronal Development and Could Explain the Cognitive Impairment in Male Patients with Distal Xq28 Copy Number Gains
PMID: 24357492
Gene: RAB39B
Disease: early-onset parkinsonism-intellectual disability syndrome
MonDO: MONDO:0010709
InheritancePattern: X-linked
Notes: Functional evidence?
Telomerase Mutations in Families with Idiopathic Pulmonary Fibrosis
PMID 17392301
Since familial idiopathic pulmonary fibrosis is also dominantly inherited, we hypothesized that telomere shortening causes this disease and that mutations in telomerase may contribute to it.
First connection between pulmonary fibrosis and TERT?
EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay
PMID: 28148688
Gene: EXTL3
Disease: Neuro-immuno-skeletal Dysplasia Syndrome
MonDO ID: n/a
OMIM: 617425
Molecular analysis of patients with aniridia in Russian Federation broadens the spectrum of PAX6 mutations T.A. Vasilyeva, T.A. Vasilyeva Federal State Budgetary Institution ‘Research Center for Medical Genetics’, Moscow, Russian FederationSearch for more papers by this authorA.A. Voskresenskaya, A.A. Voskresenskaya Department of Ambulant Surgery and Conservative Treatment, Cheboksary Branch of S. Fyodorov Eye Microsurgery Federal State Institution, Cheboksary, Russian FederationSearch for more papers by this authorB. Käsmann-Kellner, B. Käsmann-Kellner German Aniridia Center at the Section of Pediatric Ophthalmology, Orthoptics, Low Vision & Neuroophthalmology, Department of Ophthalmology, Saarland University Homburg/Saar, GermanySearch for more papers by this authorO.V. Khlebnikova, O.V. Khlebnikova Federal State Budgetary Institution ‘Research Center for Medical Genetics’, Moscow, Russian FederationSearch for more papers by this authorN.A. Pozdeyeva, N.A. Pozdeyeva Department of Ambulant Surgery and Conservative Treatment, Cheboksary Branch of S. Fyodorov Eye Microsurgery Federal State Institution, Cheboksary, Russian FederationSearch for more papers by this authorG.M. Bayazutdinova, G.M. Bayazutdinova Federal State Budgetary Institution ‘Research Center for Medical Genetics’, Moscow, Russian FederationSearch for more papers by this authorS.I. Kutsev, S.I. Kutsev Federal State Budgetary Institution ‘Research Center for Medical Genetics’, Moscow, Russian Federation Department of Molecular and Cell Genetics, Pirogov Russian National Research Medical University, Moscow, Russian FederationSearch for more papers by this authorE.K. Ginter, E.K. Ginter Federal State Budgetary Institution ‘Research Center for Medical Genetics’, Moscow, Russian FederationSearch for more papers by this authorE.V. Semina, E.V. Semina Division of Developmental Biology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WisconsinSearch for more papers by this authorA.V. Marakhonov, Corresponding Author A.V. Marakhonov marakhonov@generesearch.ru orcid.org/0000-0002-0972-5118 Federal State Budgetary Institution ‘Research Center for Medical Genetics’, Moscow, Russian Federation Laboratory of Functional Analysis of the Genome, Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow Region, Russian Federation Correspondence Rena A. Zinchenko, Andrey V. Marakhonov, Federal State Budgetary Institution ‘Research Center for Medical Genetics’, Moskvorechie Street, 1, 115478 Moscow, Russian Federation. Email: renazinchenko@mail.ru, marakhonov@generesearch.ruSearch for more papers by this authorR.A. Zinchenko, Corresponding Author R.A. Zinchenko renazinchenko@mail.ru Federal State Budgetary Institution ‘Research Center for Medical Genetics’, Moscow, Russian Federation Department of Molecular and Cell Genetics, Pirogov Russian National Research Medical University, Moscow, Russian Federation Correspondence Rena A. Zinchenko, Andrey V. Marakhonov, Federal State Budgetary Institution ‘Research Center for Medical Genetics’, Moskvorechie Street, 1, 115478 Moscow, Russian Federation. Email: renazinchenko@mail.ru, marakhonov@generesearch.ruSearch for more papers by this author
PMID 28321846
Gene: PAX6
Variant NM_001368894.2:c.-128-2del
Disease: Ocular dysgenesis
InheritancePattern: AD
Disease PAX6-related ocular dysgenesis MONDO:0800183
Proband 26.03 and apparently de novo
Mucopolysaccharidosis IVA: characterization of a common mutation found in Finnish patients with attenuated phenotype
PMID: 12721840
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
UNC80 functions as a scaffold for Src kinases in NALCN channel function
PMID 19535918 Gene: UNC80
The RAB39B p.G192R mutation causes X-linked dominant Parkinson’s disease
PMID: 26399558
Gene: RAB39B
Disease: early-onset parkinsonism-intellectual disability syndrome
MonDO: MONDO:0010709
InheritancePattern: X-linked
Mutations in EXTL3 Cause Neuro-immuno-skeletal Dysplasia Syndrome
PMID: 28132690
Gene: EXTL3
Disease: Neuro-immuno-skeletal Dysplasia Syndrome
MonDO ID: n/a
OMIM: 617425
Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients
PMID: 28708303 Gene: UNC80
Correction of MPSIVA pathology by AAV9-Galns treatment
RescueModel: Rescue WT CAG::GALNS in murine model by ovexpression in a Galns variant frequently found in human's affected with MPSIVA
GeneAlteration: transduction by AAV9 of CAG promoted WT murine optimized Galns coding sequence. Widespread tissue transduction was visualized with a CAG promoted GFP cassette delivered by AAV9, subsequently GFP production was widespread and found in all relevant tissue including osteoblast rich areas.
RescueVariant: AAV9-Galns with the coding sequence under the control of a CAG promoter element
RescuePhenotype: HP:0004325, MP:0001258, HP:0005736
RescueMethod: p.Arg386Cys (MPSIVA) mice were first transducted with CAG::GFP via AAV9 to verify efficiency of delivering the coding sequence to target tissue like bone. Then a CAG::Galns (optimized WT) was transducted in to MPSIVA mice (Galns -/-) via AAV9 by 4 weeks of age to avoid the high mortality in the Galns homozygote starting at 2 months.
RescueEvidence: Early transduction of Galns -/- mice recovered higher than WT enzyme activity and WT levels of keratan sulfate detected in liver tissue. Abnormalities in the growth plate in Galns -/- mice were absent in those treated with AAV9-Galns resulting from a return to WT levels of enzyme activity and keratan sulfate in all bone tissue sampled. GALNS activity recovered in lung and heart tissue with the elevated heart rate in MPSIVA mice returned to WT.
ModelVariant: p.Arg386Cys
Characterization of a novel exonic deletion in the GALNS gene causing Morquio A syndrome
PMID: 36245961
Gene: GALNS
Disease: Mucopolysaccharidosis IVA/ Morquio A
MonDO: MONDO:0009659
InheritancePattern: AR
Notes:
The GALNS p.P77R variant is a probable Gujarati-Indian founder mutation causing Mucopolysaccharidosis IVA syndrome
PMID: 35729508
Gene: GALNS
Disease: Mucopolysaccharidosis Type IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes: Case Study - 23 probands
Association between aplastic anaemia and mutations in telomerase RNA
PMID: 12090986
Gene: TERC
Disease: Dyskeratosis congenita & bone marrow failure/pulmonary fibrosis
MonDO: MONDO:0007485, MONDO:0013879
InheritancePattern: AD
Notes: variants: NR_001566.1:n.58G>A, NR_001566.1:n.72C>G, NR_001566.1:n.110_113del
Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma
PMID: 25217002
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Repurposing propranolol as a drug for the treatment of retinal haemangioblastomas in von Hippel-Lindau disease
PMID: 28662711
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Renal cell carcinoma in children and young adults: clinicopathological, immunohistochemical, and VHL gene analysis of 46 cases with follow-up
PMID: 20034980
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
The utility of cortical-sparing adrenalectomy in pheochromocytomas associated with genetic syndromes
PMID: 23845641
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
A unique case of renal carcinoma with Xp11.2 translocations/ TFE3 gene fusions in a 3-year-old child, with coexistent von Hippel-Lindau gene mutation
PMID: 15383938
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Case report: a synonymous VHL mutation (c.414A > G, p.Pro138Pro) causes pathogenic familial hemangioblastoma through dysregulated splicing
PMID: 32106822
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
ISOLATED PARAGANGLIOMA IN A PATIENT WITH VHL P.L163F MUTATION
PMID: 32671223
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germline mutations in the new E1' cryptic exon of the VHL gene in patients with tumours of von Hippel-Lindau disease spectrum or with paraganglioma
PMID: 31996412
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Usefulness of[111In-DTPA0] octreotide scintigraphy in a family with von Hippel-Lindau disease
PMID: 18475055
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Family history of von Hippel–Lindau disease was uncommon in Chinese patients: suggesting the higher frequency of de novo mutations in VHL gene in these patients
PMID: 22357542
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Pediatric pheochromocytoma in association with Von Hippel-Lindau disease: Focus on screening strategies
PMID: 33067065
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Genetic Study in One Individual with Brainstem Hemangioblastoma, Multiple Meningiomas and a Pituitary Space-Occupying Lesion Revealing Partial Deletion in VHL Gene
PMID: N/A
OVID: 611206512
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Monotherapy with thalidomide for treatment of spinal cord hemangioblastomas in a patient with von Hippel–Lindau disease Iacopo Sardi MD, PhD, Corresponding Author Iacopo Sardi MD, PhD i.sardi@meyer.it Department of Pediatric Hematology-Oncology, A.U.O. “Anna Meyer,” Florence, ItalyDepartment of Pediatrics, Oncology and Neuro-Surgery, “Anna Meyer” Children's Hospital, viale Pieraccini, 24, Florence 50139, Italy.===Search for more papers by this authorMassimiliano Sanzo MD, Massimiliano Sanzo MD Division of Neurosurgery, A.U.O. “Anna Meyer,” Florence, ItalySearch for more papers by this authorFlavio Giordano MD, Flavio Giordano MD Division of Neurosurgery, A.U.O. “Anna Meyer,” Florence, ItalySearch for more papers by this authorAnna Maria Buccoliero MD, Anna Maria Buccoliero MD Department of Human Pathology and Oncology, Florence, ItalySearch for more papers by this authorFederico Mussa MD, Federico Mussa MD Division of Neurosurgery, A.U.O. “Anna Meyer,” Florence, ItalySearch for more papers by this authorMaurizio Aricò MD, Maurizio Aricò MD Department of Pediatric Hematology-Oncology, A.U.O. “Anna Meyer,” Florence, ItalySearch for more papers by this authorLorenzo Genitori MD, Lorenzo Genitori MD Division of Neurosurgery, A.U.O. “Anna Meyer,” Florence, ItalySearch for more papers by this author
PMID: 19415739
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Spinal hemangioblastoma containing metastatic renal cell carcinoma in von Hippel-Lindau disease. Case report and review of the literature
PMID: 16381215
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Robotic adrenalectomy in the pediatric population: initial experience case series from a tertiary center
PMID: 33028284
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Osteoporosis and amenorrhea in a young patient with von Hippel-Lindau disease
PMID: 15658149
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Recurrent mutations in the factor IX gene: founder effect or repeat de novo events
PMID: 8365725
Gene: F9
HGNCL: 3551
PMID: 16643212
Gene: F9
HGNC: 3551
Double mutations causing haemophilia B: a double whammy!
PMID: 19236374
Gene: F9
HGNC: 3551
Molecular characterization of haemophilia B patients in southern Brazil
PMID: 28722788
Gene: F9
HGNC: 3551
Factor IX gene mutations in haemophilia B: a New Zealand population-based study
PMID: 27213901
Gene: F9
HGNC: 3551
Factor IX p.A37V mutation causes severe bleeding in a patient with phenprocoumon therapy
PMID: 34187575
Gene: F9
HGNC: 3551
Molecular pathology of haemophilia B in Turkish patients: identification of a large deletion and 33 independent point mutations
PMID: 12588353
Gene: F9
HGNC: 3551
Defective propeptide processing of blood clotting factor IX caused by mutation of arginine to glutamine at position −4
PMID: 3009023
Gene: F9
HGNC: 3551
Spectrum of F9 mutations in Chinese haemophilia B patients: identification of 20 novel mutations
PMID: 22544209
Gene: F9
HGNC: 3551
Identification of novel and recurrent mutations in Tunisian haemophilia B patients
PMID: 21118338
Gene: F9
HGNC: 3551
Targeted re-sequencing of F8, F9 and VWF: Characterization of Ion Torrent data and clinical implications for mutation screening
PMID: 31026269
Gene: F9
HGNC: 3551
Spectrum of F9 mutations in Chinese haemophilia B patients:identification of 20 novel mutations
PMID:
Gene: F9
HGNC: 3551
Mutation analysis of a cohort of US patients with hemophilia B
PMID: 24375831
Gene: F9
HGNC: 3551
Haplotype analysis of identical factor IX mutants using PCR
PMID: 1615486
Gene: F9
HGNC: 3551
Factor IX gene analysis in 70 unrelated patients with haemophilia B: description of 13 new mutations
PMID: 10595634
Gene: F9
HGNC: 3551
Why Does the Human Factor IX Gene Have a G + CContent of 40%?
PMID: 1897528
Gene: F9
HGNC: 3551
Christmas disease in a Hovawart family resembling human hemophilia B Leyden is caused by a single nucleotide deletion in a highly conserved transcription factor binding site of the F9 gene promoter
PMID: 30846504
Gene: F9
HGNC: 3551
PMID: 8772212
Gene: F9
HGNC: 3551
Severe bleeding due to hypersensitivity to vitamin K antagonist caused by the c.109G>A (p.Ala37Thr) mutation in the F9 gene in a patient with mechanical heart valve prosthesis
PMID: 30576981
Gene: F9
HGNC: 3551
Major bleeding in a patient with warfarin-hypersensitive and factor IX propeptide variant, p.Ala37Thr, who was treated with a direct oral anti-Xa inhibitor
PMID: 29923114
Gene: F9
HGNC: 3551
Effects of Exergames on Brain Dynamics in Women with Fibromyalgia: A Randomized Controlled Trial
PMID: 31336706
Gene: F8
NoEvidence: The aim of was to evaluate the effects of a 24-week "Exergame intervention" on resting brain dynamics in women with fibromyalgia in a single-blinded, randomized controlled trial. No mention of Hemophilia A or F8 gene.
Molecular Basis of Hemophilia B in Pakistan:Identification of Two Novel Mutation
PMID: None
Gene: F9
HGNC: 3551
We designed single-molecule molecular inversion probes for target selection and used next generation sequencing to sequence 87 single nucleotide polymorphisms (SNPs), coding and splice-site regions of 10 AMD-(related) genes (ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, and SLC16A8), and 3 genes that cause inherited macular dystrophies (ABCA4, CTNNA1, and PRPH2).
genotyping by "next generation sequencing to sequence 87 single nucleotide polymorphisms (SNPs), coding and splice-site regions of 10 AMD-(related) genes (ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, and SLC16A8), and 3 genes that cause inherited macular dystrophies (ABCA4, CTNNA1, and PRPH2)"
TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein
PMID: 21159800
Gene: TOPORS
Mutations of VMD2 Splicing Regulators Cause Nanophthalmos and Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC)
PMID: 15452077
Gene: BEST1
Mutations in the TOPORS gene cause 1% of autosomal dominant retinitis pigmentosa
PMID: 18509552
Gene: TOPORS
Newborn Screening for Lysosomal Storage Disorders in Illinois: The Initial 15-Month Experience
PMID: 28728811
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Mucopolysaccharidosis I mutations in Chinese patients: identification of 27 novel mutations and 6 cases involving prenatal diagnosis
PMID: 21480867
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
14/F
Case#: Patient 14, female, Han origin, 5.5 years old (age at diagnosis)
DiseaseAssertion: MPS1-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 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.266G>A (p.R89Q)
Variant1ClinVarID: 11922
Variant1CAID: CA256124
Variant2: c.266G>A (p.R89Q)
Variant2ClinVarID: 11922
Variant2CAID: CA256124
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 by parental testing.
PreviouslyPublished N/A
4
Case#: Patient No. 4 (Table 1), White race, male, 1.21 years old (age at time of gene therapy), 95 IQ score, 2.07 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
2
Case#: Patient No. 2 (Table 1), Arabic Druze ethnic group, male, 1.15 years old (age at time of gene therapy), 100 IQ score, 2.40 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.192C>A (p.Y64X)
Variant1ClinVarID: 11914
Variant1CAID: CA256113
Variant2: c.192C>A (p.Y64X)
Variant2ClinVarID: 11914
Variant2CAID: CA256113
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
7
Case#: Patient No. 7 (Table 1), Black race, male, 1.71 years (age at time of gene therapy), 80 IQ score, 1.73 years since gene therapy (1.5 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.923_926delTGCC (p.L308HfsX8)
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: c.923_926delTGCC (p.L308HfsX8)
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome
PMID: 34788506
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Five unrelated patients
Case#: 1 (Thai, male, diagnosed at age 4y)
DiseaseAssertion: MPS1
FamilyInfo: Thai, Parental consanguinity (relationship not defined)
CasePresentingHPOs: 0034337 (claw hand), 0001634 (mitral valve prolapse),
CaseHPOFreeText:
CaseNotHPOs:
CaseNotHPOFreeText: No neurologic symptoms detected
CaseEnzymeAssay: 1.97 nmole/18h/mg protein
CaseUrineGAGs:
CaseERT:
CaseBMT:
Variant1:IDUA c.*1T>C: Ex14 (p.X654Rext38)
Variant1ClinVarID:
Variant1CAID:
Variant2: IDUA c.*1T>C: Ex14 (p.X654Rext38)
Variant2ClinVarID:
Variant2CAID:
AdditionalVariants:
ParentalGenotype:
PreviouslyPublished
A novel mucopolysaccharidosis type I associated splice site mutation and IDUA splice variants
PMID: 21831683
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
PMID: 9391892
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Worldwide distribution of common IDUA pathogenic variants
This paper is not publicly available. It was obtained via an institutional account and the relevant details annotated to the PubMed abstract.
PMID: 29393969
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
genotypes of MPS I patients from 35 published studies papers
This is a review article that focuses on the prevalence of IDUA variants. The IDUA variants are not linked to specific patients or patient descriptions.
PKMPS1P9
Case#: PKMPS1P9, 1.6 years old (age at presentation), male, Pakastani
DiseaseAssertion: MPS-I
FamilyInfo: Born to a consanguineous couple
CasePresentingHPOs: Recurrent chest infections (since 1 years old), coarse facial features, umbilical hernia (HP:0002783, HP:0000256, HP:0001537)
CaseHPOFreeText: Stunted, widening of the wrist
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1277ins9 (p.[A394-L395-L396])
Variant1ClinVarID:
Variant1CAID:
Variant2: c.1277ins9 (p.[A394-L395-L396])
Variant2ClinVarID:
Variant2CAID:
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Molecular analysis of mucopolysaccharidosis type I in Tunisia: identification of novel mutation and eight Novel polymorphisms
PMID: 21521498
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
PMID: 32162878
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Implementation of an Affordable Method for MPS Diagnosis fromUrine Screening to Enzymatic Confirmation:Results of a Pilot Study in Morocco
PMID: 32162878
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
A rapid and non-invasive proteomic analysis using DBS and buccal swab for multiplexed second-tier screening of Pompe disease and Mucopolysaccharidosis type I
PMID: 35787971
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
35
Case#: Patient 35 (Table 3)
DiseaseAssertion: Attenuated naïve MPS 1
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 7 nmol/h/mg per DBS (dried blood spots) determined during NBS. 7.2 DBS protein concentration determined by Immuno-SRM (pmol/L).
CaseUrineGAGs: N/A
CaseERT: Yes
CaseBMT: N/A
Variant1: c.208C>T (p.Q70X)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2: c.299+5G>T
Variant2ClinVarID: N/A
Variant2CAID: CA549149418
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
17
Case#: 17, Male, 0.9 years (diagnosed), 3.0 years (report), 9.0 kg (weight), 66 cm (height), Iranian
DiseaseAssertion: Hurler-Scheie Syndrome
FamilyInfo: Parents are 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 0.76 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 7.8 (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
18
Case#: 18, Male, 1.3 years (diagnosed), 9.2 years (report), 20 kg (weight), 89 cm (height), Iranian
DiseaseAssertion: Scheie Syndrome
FamilyInfo: Parents are 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 1.67 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 7.7 (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
Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I
PMID: 31386236
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
14
Case#: 14, Male, 0.7 years (diagnosed), 8.5 years (report), 9.5 kg (weight), 73 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 0.6 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 6.4 (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
9
Case#: 9, Female, 0.7 years (diagnosed), 1.2 years (report), 6.8 kg (weight), 69 cm (height), Iranian
DiseaseAssertion: Hurler-Scheie Syndrome
FamilyInfo: Parents are consanguineous
CasePresentingHPOs: HP:0100790 (Hernia)
CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea
CaseNotHPOs: HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Deafness, Corneal Opacity, Hydrocephalus)
CaseNotHPOFreeText: Cardiac Manifestations
CaseEnzymeAssay: IDUA activity 0.97 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 7.21 (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
a female of Moroccan descent identified in 2017 (currently 3 years old), is homozygous for the p.P533R mutation associated with the Hurler/Scheie phenotype
Case#: P1 (IDUA-04)
DiseaseAssertion: MPS1
FamilyInfo: None provided
CasePresentingHPOs:No info
CaseHPOFreeText: No info
CaseNotHPOs: No info
CaseNotHPOFreeText: No info
CaseEnzymeAssay: Newborn screening using dried blood spot by stable isotope dilution flow injection MS/MS %IDUA enzyme activity =0.22 microM/hour
CaseUrineGAGs: Confirmatory testing using urinary GAGs (heparan [HS] and dermatan sulfate [DS] by LS-MS/MS method: DS=2.5 mg/L, HS=0.89 mg/L
CaseERT: Started ERT (100 U/kg/Week) withing 15 days of birth
CaseBMT: No info
Variant1:p.P533R
Variant1ClinVarID:11910
Variant1CAID:
Variant2: p.P533R
Variant2ClinVarID:11910
Variant2CAID:
AdditionalVariants:
ParentalGenotype: No info
PreviouslyPublishedNot stated
“Missing mutations” in MPS I: Identification of two novel copy number variations by an IDUA‐specific in house MLPA assay
PMID: 31319022
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
16
Case#: Patient 16, female, 1 year and 3 months (age at presentation).
DiseaseAssertion: MPS1-H/S
FamilyInfo: Consanguinity in the family present for this patient.
CasePresentingHPOs: Corneal clouding, coarse facial features, cardiomyopathy, dystosis multiplex (HP:0007957, HP:0000256, HP:0001638, HP:0000943)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.972-1G>T
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: c.972-1G>T
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series
PMID: 27196898
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Mucopolysaccharidosis type I: identification of 8 novelmutations and determination of the frequency of thetwo common a-L-iduronidase mutations (W402X andQ70X) among European patients
PMID: 7951228
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
c.1A > G
Case#: No additional case information provided
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.1A>G (p.M1?)
Variant1ClinVarID: 1323098
Variant1CAID: CA355945206
Variant2: c.1A>G (p.M1?)
Variant2ClinVarID: 1323098
Variant2CAID: CA355945206
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
IDUA gene mutations in mucopolysaccharidosis type-1 patientsfrom two Pakistani inbred families
PMID: 31400021 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive
A Novel IDUA Mutation Causing Ocular Disease in 2 Siblings
PMID: 36951468
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Segmental and total uniparental isodisomy (UPiD) as a disease mechanism in autosomal recessive lysosomal disorders: evidence from SNP arrays
PMID: 30737479
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Hurler disease (mucopolysaccharidosis type IH): clinical features and consanguinity in Tunisian population
PMID: 22074387
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Bone Remodeling in an Mps-1h Girl after Hematopoietic Stem Cell Transplantation along with Enzymatic Replacement Therapy
PMID: 35619307
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Identification and characterization of -3c–g acceptor splice site mutation in human α- l-iduronidase associated with mucopolysaccharidosis type IH/S
PMID: 10735634
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
The impact of laronidase treatment inotolaryngological manifestations of patientswith mucopolysaccharidosis
PMID: 26750310 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive
Hurler
Case#: <0.1% residual activity at 37 °C
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: <0.1 nmol/mg/h IDUA activity at 37 °C
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.134del12 on paper but nomenclature is c.46_57del (p.Ser16_Ala19del)
Variant1ClinVarID: 92643
Variant1CAID: CA220509
Variant2: c.134del12 on paper but nomenclature is c.46_57del (p.Ser16_Ala19del)
ClinVarID: 92643
Variant2CAID: CA220509
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Insights into Mucopolysaccharidosis I from the structure and action of α-L-Iduronidase
PMID: 24036510
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Why Insufficient: Variants are not linked to probands. This paper is assessing IDUA mutations on the structure of alpha-L-iduronidase. Therefore they are pulling common IDUA variants and using them to assess structure, rather than investigating how a variant has impacted a proband.
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: H82Q
Variant1ClinVarID:
Variant1CAID: CA355946477
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Patient 1
Case#: Patient 1, male, 1 year old (age at diagnosis), 2 years old (age when deceased - due to a severe respiratory infection)
DiseaseAssertion: MPS I-H
FamilyInfo: Parents had a consanguineous marriage
CasePresentingHPOs: Coarse facial features, corneal clouding, hepatosplenomegaly, skeletal dysplasia, global developmental delay (HP:0000280, HP:0007957, HP:0001433, HP:0002652, HP:0001263)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.252insC (current nomenclature: c.252dup)
Variant1ClinVarID: N/A
Variant1CAID: CA3060586149
Variant2: c.252insC (current nomenclature: c.252dup)
Variant2ClinVarID: N/A
Variant2CAID: CA3060586149
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Lower Exposure to Busulfan Allows for StableEngraftment of Donor Hematopoietic Stem Cells inChildren with Mucopolysaccharidosis Type I: A CaseReport of Four Patients
PMID: 32781600 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive
Implementation of an Affordable Method for MPS Diagnosis from Urine Screening to Enzymatic Confirmation: Results of a Pilot Study in Morocco
PMID: 32162878
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Novel frameshift variant in the IDUA gene underlies Mucopolysaccharidoses type I in a consanguineous Yemeni pedigree
PMID: 28649516
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Hematopoietic differentiation of induced pluripotent stem cells from patients with mucopolysaccharidosis type I (Hurler syndrome)
PMID: 21037085
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Successful pregnancy and breastfeeding in a woman with mucopolysaccharidosis type I while receiving laronidase enzyme replacement. therapy
PMID: 25864295
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Epidemiology of Mucopolysaccharidoses Update
PMID: 33578874
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Anthropometric data of 14 patients with mucopolysaccharidosis I: retrospective analysis and efficacy of recombinant human alpha-L-iduronidase (laronidase)
PMID: 19783188
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Agreement between the results of meta-analyses from case reports and from clinical studies regarding the efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age: An example of case reports meta-analyses as an useful tool for evidence-based medicine in rare diseases
Free, full-text NOT available. Full text was retrieved via a university account, and the free PubMed abstract was annotated.
This paper describes a meta-analysis of previously published data for 11 patients. PMID's for prior published reports:
25864295, 21482163, 22303797, 21167740, 19894140, 18792977, 18546328, 16601901
The above PMID's are all included in the IDUA Excel file.
Three cited manuscripts do not have a PMID and are not included in the IDUA Excel file. Links to these papers are provided below:
https://doi.org/10.1016/j.farma.2010.11.005 (in Spanish)
Mutational Analysis of the alpha-L-iduronidase gene in three Egyptian families: identification of three novel mutations and five novel polymorphisms
PMID: 19839758
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Molecular characterization of a large cohort of Mucopolysaccharidosis patients: Iran Mucopolysaccharidosis RE-diagnosis Study (IMPRESsion)
PMID: 35005816
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
High Precision Newborn Screening for Mucopolysaccharidosis Type I by Enzymatic Activity followed by Endogenous, Non-Reducing End Glycosaminoglycan Analysis
PMID: 39645522
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Type 2M Von Willebrand Disease: A Case Report
Case: 24-year-old Caucasian woman with a rare variety of type 2M VWD
DiseaseAssertion: 2M VWD
FamilyInfo: family history was negative for easy bruisability, bleeding, or clotting disorder but maternal grandmother had lung cancer.
CaseNOTHPOFreeText: Von Willebrand factor antigen 45% on 9/12/17 and 37% on 9/19/17 with the ratio of VWF activity to the antigen is less than 0.7
ParentalGenotype(s):Unknown
CasePresentingHPOs: HP:0003010 (Prolonged bleeding time), HP:0000978 (Bruising susceptibility).
**CaseHPOFreeText: ** loss of weight over the last six months, The complete blood count, comprehensive metabolic panel, factor VIII, prothrombin time and partial thromboplastin time, D-Dimer, and antithrombin activity were normal. Her von Willebrand factor activity was much lower compared to the antigen.
CasePreviousTesting: None
GenotypingMethod: Patient have not been genotyped
PreviouslyPublished: N/A
Variant: N/A
ClinVarID: N/A
gnomAD: N/A
**Gene: ** VWF Inheritance mode autosomal dominant variety with normal, high molecular weight multimers
1
Case: 2M-2
DiseaseAssertion: VWD2M
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: AcuStar RCo/Ag = 0.01; AcuStar CB/Ag = 1.16; ELISA CB/Ag = 1.41
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: not described
PreviouslyPublished: 1409710
Gene: VWF
Variant: c.3970G>A (p.Gly1324Ser)
HGVS: NM_000552.5(VWF):c.3970G>A (p.Gly1324Ser)
ClinVarID: 300; https://www.ncbi.nlm.nih.gov/clinvar/variation/300/?new_evidence=false
CAID:
gnomAD: MAF = 0.00003267 in South Asian population; https://gnomad.broadinstitute.org/variant/12-6128614-C-T
0.36
Case: 2A-5
DiseaseAssertion: VWD2A
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: AcuStar RCo/Ag = 0.36; AcuStar CB/Ag = 0.15; ELISA CB/Ag = 0.24
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: not described
PreviouslyPublished: PMID: 1537829
Gene: VWF
Variant: c.4789C>T (p.Arg1597Trp)
HGVS: NM_000552.5(VWF):c.4789C>T (p.Arg1597Trp)
ClinVarID: 285; https://www.ncbi.nlm.nih.gov/clinvar/variation/285/?new_evidence=false
CAID:
gnomAD: absent
1
Case: 2B-8
DiseaseAssertion: VWD2B
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: AcuStar RCo/Ag = 0.99; AcuStar CB/Ag = 1.35; ELISA CB/Ag = 1.02
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: not described
PreviouslyPublished: 16985174
Gene: VWF
Variant: c.3797C>T (p.Pro1266Leu)
HGVS: NM_000552.5(VWF):c.3797C>T (p.Pro1266Leu)
ClinVarID: 314; https://www.ncbi.nlm.nih.gov/clinvar/variation/314/?new_evidence=false
CAID:
gnomAD: MAF (European, Finnish) = 0.003667; 1 homozygote; https://gnomad.broadinstitute.org/variant/12-6128787-G-A
1
Case: 2A-7
DiseaseAssertion: VWD2A
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: AcuStar RCo/Ag = 0.27; AcuStar CB/Ag = 0.10; ELISA CB/Ag = 0.39
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: not described
PreviouslyPublished: PMID:1673047
Gene: VWF
Variant: c.4883T>C (p.Ile1628Thr)
HGVS: NM_000552.5(VWF):c.4883T>C (p.Ile1628Thr)
ClinVarID: 284; https://www.ncbi.nlm.nih.gov/clinvar/variation/284/?new_evidence=false
CAID:
gnomAD: absent
0.49
Case: 2A-1
DiseaseAssertion: VWD2A
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: AcuStar RCo/Ag = 0.49; AcuStar CB/Ag = 0.29; ELISA CB/Ag = 0.33
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: not described
PreviouslyPublished: PMID: 8435341
Gene: VWF
Variant: c.4541T>G (p.Phe1514Cys)
HGVS: NM_000552.5(VWF):c.4541T>G (p.Phe1514Cys)
ClinVarID: 304; https://www.ncbi.nlm.nih.gov/clinvar/variation/304/?new_evidence=false
CAID:
gnomAD: absent
9
Case: Patient 9 (Family B), male, 71yo
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 = 56, PFA 100 sec = >300, SPA % = 22, MADR mg/mL = 0.3, VWF:Ag U/dL = 81.2, VWF:CB U/dL = 25.9, VWF:CB ratio = 0.32, VWF:RCo U/dL = 33.75, VWF:RCo ratio = 0.41, Platelet VWF U/dL = 146.2, FVIII U/dL = 52, BAT F/M = NA
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
3
Case: Patient 3 (Family B), male, 55yo
DiseaseAssertion: VWD2B
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147
(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 = 204, PFA 100 sec = >300, SPA % = 0, MADR mg/mL = 0.45, VWF:Ag U/dL = 23.4, VWF:CB U/dL = 21.1, VWF:CB ratio = 0.9, VWF:RCo U/dL = 17.2, VWF:RCo ratio = 0.74, Platelet VWF U/dL = 42.6, FVIII U/dL = 60.5, BAT F/M = 20
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: Sequencing of exon 28 of VWF
PreviouslyPublished: NA
Gene: VWF
Variant 1: c.3797C>T (p.Pro1266Leu)
HGVS: NM_000552.4(VWF):c.3797C>T (p.Pro1266Leu)
ClinVarID: 314; https://www.ncbi.nlm.nih.gov/clinvar/variation/314/
CAID: NA
gnomAD: MAF = 0.003667 (92/25086 alleles; 1 homozygote) in the European (Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128787-G-A?dataset=gnomad_r2_1
Variant 2: c.7085G>T (p.Cys2362Phe)
HGVS: NM_000552.4(VWF):c.7085G>T (p.Cys2362Phe)
ClinVarID: 315; https://www.ncbi.nlm.nih.gov/clinvar/variation/315/
CAID: NA
gnomAD: absent
a 5-year-old boy was diagnosed with mild hemophilia A
Case#: Male, 31<br /> DiseaseAssertion: VWD 2N<br /> FamilyInfo: A younger brother with mild HA, sister with normal VWF levels, no other famile members with bleeding disorders<br /> ParentalGenotype: <br /> CasePresentingHPOs: HP:0000421 (epistaxis), HP:0007420 (spontaneous hematoma)<br /> CaseHPOFreeText: Soft tissue bleeding, VWF:Ag 80%, VWF:RCo 60%, normal VWF multimer pattern<br /> CaseNotHPOs:<br /> CaseNotHPOFreeText: <br /> CasePreviousTesting: Genotyping using Next Gen screening, by Sanger sequence screening of all 26 exons of F8 gene, by a multiplex ligation-dependent probe affinity assay, and by a VWF:FVIII binding assay<br /> Gene: VWF<br /> Variant: c2390T>G in exon 18<br /> ClinVar:<br /> CAID: gnomAD:
Combined effects of two mutations in von Willebrand disease 2M phenotype
PMID: 30046717
Gene: von Willebrand Factor (VWF)
Case: P10, Chinese, male, 5yo
DiseaseAssertion: VWD1
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type A blood, bleeding score = 2; VWF:Ag (%) = 4.2, VWF:RCo (%) = 3.8, FVIII:C (%) = 30.1, VWF:CB (%) = 3.5, VWFpp (%) = 4.1, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.8, VWFpp/VWF:Ag = 1.0, FVIII:C/VWF:Ag = 7.4, RIPA (1.2 mg/ml, %) = 40.1
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant 1: c.7199delA (p.Asn2400Thrfs*4) - Unregistered Variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Variant 2: c.8155+5G>C - Unregistered Variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Case: P72, Chinese, female, 25yo
DiseaseAssertion: VWD2B
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type A blood, bleeding score = 7; VWF:Ag (%) = 31.1, VWF:RCo (%) = 10.5, FVIII:C (%) = 44.8, VWF:CB (%) = 5.4, VWFpp (%) = 73, VWF:RCo/VWF:Ag = 0.3, VWF:CB/VWF:Ag = 0.2, VWFpp/VWF:Ag = 2.3, FVIII:C/VWF:Ag = 1.4, RIPA (0.5 mg/ml, %) = 8.7, PLT(×109/l) = 181
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.3939G>C (p.Trp1313Cys)
HGVS: NM_000552.4(VWF):c.3939G>C (p.Trp1313Cys)
ClinVarID: 287; https://www.ncbi.nlm.nih.gov/clinvar/variation/287/
CAID: NA
gnomAD: absent
Case: P34, Chinese, female, 34yo
DiseaseAssertion: VWD2B
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type O blood, bleeding score = 13; VWF:Ag (%) = 20.2, VWF:RCo (%) = 6.9, FVIII:C (%) = 32.9, VWF:CB (%) = 4.8, VWFpp (%) = 54.5, VWF:RCo/VWF:Ag = 0.3, VWF:CB/VWF:Ag = 0.2, VWFpp/VWF:Ag = 2.7, FVIII:C/VWF:Ag = 1.6, RIPA (0.5 mg/ml, %) = 65.1, PLT(×109/l) = 153
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
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
Case: P36, Chinese, male, 56yo
DiseaseAssertion: VWD3
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type A blood, bleeding score = 10; VWF:Ag (%) = 1.0, VWF:RCo (%) = 0.9, FVIII:C (%) = 4.1, VWF:CB (%) = 0.9, VWFpp (%) = 0.9, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.9, VWFpp/VWF:Ag = 0.9, FVIII:C/VWF:Ag = 4.1
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.5870delA - unregistered variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Case: P29, Chinese, male, 10yo
DiseaseAssertion: VWD2M
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type B blood, bleeding score = 5; VWF:Ag (%) = 13.9, VWF:RCo (%) = 5.9, FVIII:C (%) = 37.8, VWF:CB (%) = 17.4, VWFpp (%) = 31.3, VWF:RCo/VWF:Ag = 0.4, VWF:CB/VWF:Ag = 1.3, VWFpp/VWF:Ag = 2.3, FVIII:C/VWF:Ag = 2.7
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.3943C>T (p.Arg1315Cys)
HGVS: NM_000552.4(VWF):c.3943C>T (p.Arg1315Cys)
ClinVarID: 100310; https://www.ncbi.nlm.nih.gov/clinvar/variation/100310/
CAID: NA
gnomAD: absent
Case: P22, Chinese, male, 22yo
DiseaseAssertion: VWD3
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type O blood, bleeding score = 10; VWF:Ag (%) = 1.4, VWF:RCo (%) = 1.2, FVIII:C (%) = 5.1, VWF:CB (%) = 1.3, VWFpp (%) = 1.0, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.9, VWFpp/VWF:Ag = 0.7, FVIII:C/VWF:Ag = 3.6
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.8116–2delA - Unregistered variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Case: P42, Chinese, male, 10yo
DiseaseAssertion: VWD1
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type O blood, bleeding score = 1; VWF:Ag (%) = 41.9, VWF:RCo (%) = 33.9, FVIII:C (%) = 54.7, VWF:CB (%) = 46.8, VWFpp (%) = 34.6, VWF:RCo/VWF:Ag = 1.0, VWF:CB/VWF:Ag = 1.1, VWFpp/VWF:Ag = 0.8, FVIII:C/VWF:Ag = 1.3
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.-672C>T
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Coagulation Testing in the Core Laboratory
PMID: 29126301
Gene: VWF
HGNC: 12726 (type 1)
Note: This article is about platelet coagulation and how to test it.
2B
Case: 2B, male, 55yo
DiseaseAssertion: VWD2B
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs:
CaseHPOFreeText: Blood type: O+, bleeding score = 17, VWF:Ag (IU/mL) = 0.40; VWF:RCo (IU/mL) = 0.13; FVIII:C (IU/mL) = 0.46
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: qRT-PCR
PreviouslyPublished:
Gene: VWF
Variant: c.3946G>A (p.Val1316Met)
HGVS: NM_000552.5(VWF):c.3946G>A (p.Val1316Met)
ClinVarID: 290; https://www.ncbi.nlm.nih.gov/clinvar/variation/290/?new_evidence=false
CAID:
gnomAD: absent
Bleeding score in Type 1 von Willebrand disease patients using the ISTH-BAT questionnaire A. Pathare, Corresponding Author A. Pathare avp16@hotmail.com orcid.org/0000-0003-3205-0611 Department of Haematology, College of Medicine & Health Sciences, Sultan Qaboos University Hospital, Muscat, Oman Correspondence Dr. Anil Pathare, Department of Haematology, Sultan Qaboos University Hospital, Muscat, Oman. Email: avp16@hotmail.comSearch for more papers by this authorS. Al Omrani, S. Al Omrani Department of Haematology, College of Medicine & Health Sciences, Sultan Qaboos University Hospital, Muscat, OmanSearch for more papers by this authorF. Al Hajri, F. Al Hajri Department of Haematology, College of Medicine & Health Sciences, Sultan Qaboos University Hospital, Muscat, OmanSearch for more papers by this authorN. Al Obaidani, N. Al Obaidani Department of Haematology, College of Medicine & Health Sciences, Sultan Qaboos University Hospital, Muscat, OmanSearch for more papers by this authorB. Al Balushi, B. Al Balushi Department of Haematology, College of Medicine & Health Sciences, Sultan Qaboos University Hospital, Muscat, OmanSearch for more papers by this authorK. Al Falahi, K. Al Falahi Department of Haematology, College of Medicine & Health Sciences, Sultan Qaboos University Hospital, Muscat, OmanSearch for more papers by this author
PMID: 29115727
Gene: VWF
HGNC: 12726 (type 1)
Note: This article is about how the median ISTH-BAT questionnaire score for VWD type 1 was 7 (IQR; 2,11).
P6
Case: P6, F/7
DiseaseAssertion: VWD1
FamilyInfo: No family history
ParentalGenotype: NA
CaseHPOFreeText: The bleeding score was 5, aPTT was 29 seconds, FVIII:C was 71%, VWF:RCo was 19 IU/dL, and VWF:Ag was 19 IU/dL, with a VWF:RCo/VWF:Ag ratio of 1.0. The VWF multimer pattern was normal, RIPA was not tested, and the platelet count was 475 × 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:
Clinical and Laboratory Phenotype Variability in Type 2M Von Willebrand Disease
PMID: 28544236
Gene VWF
His mother also had a history of epistaxis, menorrhagia and anemia
Case: Patient IV-4, Female (mother of proband V-2) DiseaseAssertion: Type 2A VWD, based on history of abnormal bleeding, low plasma VWF:Ag and activity, and lack of plasma HMW VWF multimers. FamilyInfo: Mother of proband V-2; part of 5-affected-member pedigree (Fig. 1). ParentalGenotype(s): Not described (her own parents' genotype status not reported in extracted text — see Figure 1). CasePresentingHPOs: HP:0000421 (Epistaxis), HP:0000132 (Menorrhagia), HP:0012147 (Reduced quantity of VWF; VWF:Ag 21.7 U/dL), HP:0030129 (Impaired VWF:RCo; VWF:Rco 5.0 U/dL), HP:0030132 (Absence of large VWF multimers — plasma), HP:0011871 (Impaired RIPA; 3.0%), HP:0003645 (Prolonged partial thromboplastin time; APTT 46.1 sec) CaseHPOFreeText: Anemia (secondary to menorrhagia; no matching HPO code in the approved list); FVIII:C not tested (N/A); TT 18.1 sec and PT 14.1 sec both within normal range. CaseNOTHPOs: NA CaseNOTHPOFreeText: Platelet VWF multimer status NOT tested for this patient ("Platelet samples were not available from IV-4") — do not assume the "normal platelet multimers" finding reported for the other four affected members applies here. CasePreviousTesting: Targeted confirmation of the familial VWF variant (not described as independent full 52-exon screening for this individual specifically); not genome-wide. GenotypingMethod: Sanger sequencing/allele-specific analysis, same platform as proband (Applied Biosystems 310 DNA analyzer). 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
IV-2
Case: Patient IV-2 (daughter 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: Daughter 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 30.4 U/dL), HP:0030129 (Impaired VWF:RCo; VWF:Rco 8.4 U/dL), HP:0030132 (Absence of large VWF multimers — plasma), HP:0003645 (Prolonged partial thromboplastin time; APTT 45.8 sec) CaseHPOFreeText: Described only generically as having "abnormal bleedings" / "similar clinical symptoms" — no itemized bleeding symptoms given specifically for this individual. FVIII:C 50.0 U/dL — at the exact lower limit of normal (nv 50-150), notably higher than the other affected members. RIPA not tested (N/A). TT 15.6 sec and PT 13.8 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
20
Case#: Subject number 20, female, 29 years (diagnosis), 40 years (baseline visit), 40 years (ERT), 39 (age at ventilation)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)
CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit
CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)
CaseNotHPOFreeText:
CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"
PreviouslyPublished: N/A
26
Case#: Subject number 26, male, 35 years (diagnosis), 51 years (baseline visit), 51 years (ERT), 49 (age at ventilation)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)
CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit
CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)
CaseNotHPOFreeText:
CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"
PreviouslyPublished: N/A
15
Case#: Subject number 15, female, 35 years (diagnosis), 51 years (baseline visit), 46 years (ERT), 46 (ventilation)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)
CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit
CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)
CaseNotHPOFreeText:
CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"
PreviouslyPublished: N/A
24
Case#: Subject number 24, female, 42 years (diagnosis), 57 years (baseline visit), 55 years (ERT), 54 (age at ventilation)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)
CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit
CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)
CaseNotHPOFreeText:
CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"
PreviouslyPublished: N/A
27
Case#: Subject number 27, male, 35 years (diagnosis), 51 years (baseline visit)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0001324 (Muscle Weakness)
CaseHPOFreeText:
CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)
CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit
CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"
PreviouslyPublished: N/A
11
Case#: Subject number 11, male, 23 years (diagnosis), 31 years (baseline visit), 24 years (ERT), 23 (ventilation)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)
CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit
CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)
CaseNotHPOFreeText:
CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"
PreviouslyPublished: N/A
12
Case#: Subject number 12, female, 20 years (diagnosis), 46 years (baseline visit), 39 years (ERT)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0001324 (Muscle Weakness)
CaseHPOFreeText:
CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)
CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit
CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"
PreviouslyPublished: N/A
29
Case#: Subject number 29, female, 40 years (diagnosis), 54 years (baseline visit), 48 (ERT)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0001324 (Muscle Weakness)
CaseHPOFreeText:
CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)
CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit
CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"
PreviouslyPublished: N/A
Case 1
Case#: Case 1, Boy, Death at 6-7 months old, Hispanic
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0002240, HP:0001640, 0000961, HP:0002090, HP:0001270, HP:0031664, HP:0200128, HP:0001252
(Hepatomegaly, Cardiomegaly, Cyanosis, Pneumonia, Motor delay, Systolic heart murmur, Biventricular hypertrophy, Muscular Hypotonia)
CaseHPOFreeText: Heart failure, Systolic murmur grade II-III, Enlarged, EKG showed an inverted T wave from V4-V6 as well as AVF, suggesting left systolic overload.
CaseNotHPOs:
CaseNotHPOFreeText:
CasePreviousTesting: Ejection fraction of 52%
Serum creatine kinase was 386 IU/L (mildly elevated)
GAA activity on dried blood spot was decreased (1.08 nmol/L; normal range: 1.5-10 nmol/L)
Whole exon and exon-intron boundaries direct sequencing revealed a homozygous single base deletion c.1987delC
Variant: c.1987delC
ClinVar: N/A
CAID: N/A
gnomAD: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
Arab
Case2: Arab Patient (found in the GT database) gender and age are not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000421, HP:0000225, HP:0002239, HP:0000132, HP:0000967, HP:0000979, HP:0006298
(Epistaxis, gingival bleeding, GI bleeding, menorrhagia, petechiae/purpura, prolonged , bleeding after tooth extraction)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: <2% of normal GPIIIa and GPIIb surface expression
PlateletAggregation: N/A
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: IVS(-3)-418del (May be registered; however, need to consult senior biocurator)
LegacyVariant: ^
ClinVar: ^
CAiD: ^
gnomAD: ^
PreviouslyPublished: References 8-12
Amsterdam
PreviouslyPublished: PMID: 8471765
This proband has been previously published in the PMID listed above --> see that paper to get patient information. This patient can also be found in the GT database
Glanzmann Thrombasthenia Due to a Two Amino Acid Deletion in the Fourth Calcium-Binding Domain of αIIb: Demonstration of the Importance of Calcium-Binding Domains in the Conformation of αIIbβ3
PMID: 8704171
Gene: ITA2B
HGNC: 6138
Catheter Intervention in a Patient with Intracranial Aneurysms and Glanzmann Thrombasthenia Caused by a Novel Homozygous Likely Pathogenic Variant in the ITGA2B Gene
PMID: 39057107
Gene: ITGA2B
GNC: 6138
F8.I.2
Case#: Female, 75 (age when studied in 1975)
Disease: Glazmann's Thrombasthenia Like Syndrome
CasePresentingHPOs: HP:0001873, HP:0006298
Thrombocytopenia, Prolonged bleeding after dental extraction
CaseNotHPOs: NA
FamilyInfo: Pedigree figure 1. Several affected family members.
PlateletAgreggation:Daughter studied: Decreased PLT aggregation and diminished ATP release with the agonists ADP, collagen, and AA, with normal ristocetin agglutination
GenotypingMethod: Genetic analysis of ITGA2B and ITGB3 genes was performed by next-generation sequencing (NGS). Sanger sequencing used to confirm variants.
From Daughter
ClinVar: Not Found
CAID: CA400034393
Variant: NM_000212.3:c.2278C>T (ITGB3)
GnomAD: Not Found
ExpressionEvidence: Level of expression on PLT surface determined by FCM: CD41a (GPIIb/IIIa) 52%, CD61 (GPIIIa) 77%, and CD42b (GPIb) 129%. Healthy control value range: CD41a (GPIIb/IIIa) (85-115%); CD61 (GPIIIa) (80-120%); CD42b (GPIb) (70-130%).
F9.II.2
Case#: Female, 37 (age when studied)
Disease: Glazmann's Thrombasthenia Like Syndrome
CasePresentingHPOs: HP:0001873, HP:0000978, HP:0000225
Thrombocytopenia, bruising susceptibility, gingival bleeding
CaseNotHPOs: NA
FamilyInfo: Pedigree figure 1. Several affected family members, history of thrombocytopenia.
PlateletAgreggation:Sister studied: Decreased PLT aggregation and diminished ATP release with the agonists ADP, collagen, and AA, with normal ristocetin agglutination
GenotypingMethod: Genetic analysis of ITGA2B and ITGB3 genes was performed by next-generation sequencing (NGS). Sanger sequencing used to confirm variants.
ClinVar: Not Found
CAID: CA400034393
Variant: NM_000212.3:c.2278C>T (ITGB3)
GnomAD: Not Found
ExpressionEvidence: Level of expression on PLT surface determined by FCM: CD41a (GPIIb/IIIa) 73%, CD61 (GPIIIa) 74%, and CD42b (GPIb) 111%. Healthy control value range: CD41a (GPIIb/IIIa) (85-115%); CD61 (GPIIIa) (80-120%); CD42b (GPIb) (70-130%).
Single Point Mutation in Human Glycoprotein IIIa Is Associated With a New Platelet-Specific Alloantigen (Mo) Involved in Neonatal Alloimmune Thrombocytopenia
PMID: 8093349
Gene: ITGB3
HGNC: 6156
GT6
Case6: GT-6, Croats, gender or age not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1
PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned
CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.
Gene: ITGB3
Variant: NM_000212.2:c.166–2A>G
LegacyVariant: N/A
ClinVar: N/A
CAiD: Unregistered Variant
gnomAD: N/A
Single-Strand Conformation Polymorphism Analysis Is a Rapid and Effective Method for the Identification of Mutations and Polymorphisms in the Gene for Glycoprotein IIIa
PMID: 8400280
Gene: ITGB3
HGNC: 6156
A novel frameshift mutation in the ITGB3 gene leading to Glanzmann's thrombasthenia in a Saudi Arabian family
PMID: 33600779
The propositus (A.C.S.; II.1) in family 1 is a 22-yearold Portuguese girl
Case1: Female, 22 years old, Portugese
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Also studied were the patient’s mother (I.2),her father (1.1), and her sister (II.2). Of these family members, only her sister has reported excessive bleeding although platelet aggregation tests were normal for all of them. Consanguinity was present as her parents were cousins.
ParentalGenotype: Parents heterozygous for mutation
CasePresentingHPOs: HP:0000967
(Petechia)
CaseHPOFreeText: Mucocutaneous bleeding
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
ProteinExpression: <5% surface expression of aIIbb3
PlateletAggregation: Absent with physiologic agonists but agglutination with ristocetin was normal
CasePreviousTesting: We examined each of the 30 exons of the b3 gene and each of the 15 exons of the aIIb gene for migration changes in PCR-SSCP analysis
Gene: ITGB3
Variant:
LegacyVariant:
ClinVar:
CAiD:
gnomAD: N/A
Characterization of New ACADSB Gene Sequence Mutations and Clinical Implications in Patients with 2-Methylbutyrylglycinuria Identified by Newborn Screening
PMID: 20547083
Gene: ACADSB
Disease: 2-methylbutyrylglycinuria
MonDO: MONDO:0012392
InheritancePattern: AR
Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations
Gene: CPS1
MONDO:0009376
carbamoyl phosphate synthetase I deficiency disease
Inheritance: Autosomal recessive
PMID 21120950
Understanding N‐Acetyl‐L‐Glutamate Synthase Deficiency: Mutational Spectrum, Impact of Clinical Mutations on Enzyme Functionality, and Structural Considerations
PMID: 27037498
Gene: NAGS
MonDO: MONDO:0009377
InheritancePattern: AR
Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia
PMID: 18241071
Gene: PAX6
Variant NM_001368894.2:c.-128-2del
Disease: Ocular dysgenesis
InheritancePattern: AD
Disease PAX6-related ocular dysgenesis MONDO:0800183
X-linked Parkinsonism with Intellectual Disability caused by novelmutations and somatic mosaicism inRAB39Bgene
PMID: 28851564
Gene: RAB39B
Disease: early-onset parkinsonism-intellectual disability syndrome
MonDO: MONDO:0010709
Extension of the mutation spectrum of PAX6 from three Chinese congenital aniridia families and identification of male gonadal mosaicism
PMID: 30334364
Variant NM_000280.5:c.1123C>A (p.Pro375Thr)
Gene: PAX6
Disease: Ocular dysgenesis
InheritancePattern: AD
Hexb enzyme deficiency leads to lysosomal abnormalities in radial glia and microglia in zebrafish brain development
PMID: 31140649
Gene: HEXB
Disease: Sandhoff Disease
MonDO: MONDO:0010006
Loss of human ICOSL results in combined immunodeficiency
PMID: 30498080
Gene: ICOSLG
Disease: Combined Immunodeficiency
MonDO: MONDO:0015131
InheritancePattern: Autosomal recessive pattern
Shi, 2016 - A novel RAB39B gene mutation in X-linked juvenile parkinsonism with basal ganglia calcification
PMID: 27943471
Gene: RAB39B
Disease: early-onset parkinsonism-intellectual disability syndrome
MonDO: MONDO:0010709
A new PAX6 mutation in familial aniridia
PMID: 7666404
Variant NM_001368894.2:c.1225G>C(p.Gly409Arg)
Gene: PAX6
Disease: Ocular dysgenesis
InheritancePattern: AD
Notes SNP at last nucleotide in exon 13 leads to loss of donor site and exon skipping event.
Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80
PMID 19092807 Gene: UNC80
RNA analysis of the GALNS transcript reveals novel pathogenic mechanisms associated with Morquio syndrome A
PMID: 35782621
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes:
Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.
PMID: 1522213
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
ExperimentName: Expression of variant carrying cDNA in GALNS deficient fibroblasts
FunctionalEvidence: cDNA encoding each of the 15 variants identified in the study were transfected into a GALNS deficient fibroblast cell line. 14 of the 15 altered cDNA's showed no increase in GALNS activity when the cells were assayed, confirming a lack of enzymatic activity.
HGNC:
GeneEvidence:
SharedGeneImplication:
We identified an Australian kindred with three brothers who presented in childhood with nonprogressive intellectual disability (ID), which included delayed developmental milestones, cognitive impairment, and macrocephaly
Case#: Wilson_Australian kindred_Person II:2
Demographics: Male, 44y at diagnosis, Australia
CasePresentingHPOs: HP:0000750, HP:0001249, HP:0007351, HP:0002362, HP:0002067, HP:0100660, HP:0002396, HP:0000256
Age at onset <2y, while age at tremor onset was 38y. Birth and early milestones were normal. Early learning difficulties were reported and the proband was able to read and write. Parkinsonism classification was akinetic-rigid. Proband showed L-Dopa response, hypokinetic dysarthria, and normal cerebellar function. Other normal features included normal eye examination, MRI, Fragile X testing, karyotype, Copper testing, blood count and chemistry, urine metabolic testing and hearing.
CaseNotHPOs:
CasePreviousTesting: Linkage analysis using homozygous recessive model identified no linkage to autosomes, but to two regions: Xp22.2 and Xq27.3–qter
CaseMethod1: Copy number variation analysis
CaseMethod2: PCR
CaseGenotypingMethod: A ~45-kb deletion within the Xq haplotype was identified that encompassed the complete RAB39B gene and the last 3 coding exons of CLIC2.
Variant: NC_000023.11:g.(155246216_?)_(?_155288781)del
ClinVar: 157665
CAID:
gnomAD:
VariantEvidence: The proband was hemizygous for the ~45-kb deletion encompassing the complete RAB39B and partial CLIC2 genes. Expression of both transcripts was absent from fibroblast cells of affected individuals. The proband is not scored any points as the variant involves deletion of part of an additional gene, CLIC2. Although the authors ruled out seizures and cardiac anomalies (phenotypes associated with CLIC2 missense variant) in patients from the family, it is not conclusive that CLIC2 deletion does not have any impact on the proband's phenotype.
CaseAddInfo: The proband's siblings were also similarly affected. Elder brother of the proband died at 48y from positional asphyxia, and postmortem neuropathological studies on proband's brain showed pallor of the substantia nigra and locus coeruleus. H&E staining of substantia nigra revealed PD features, including loss of pigmented neurons and Lewy bodies in surviving neurons. Abundance of cortical Lewy bodies, were noted. Tau-immunoreactive NFTs were also observed in a small proportion of the surviving pigmented SN neurons
CasePMIDs:
phenotype of the Australian kindred is similar to the basal ganglia disorder (Waisman syndrome [MIM 311510]) reported for a Wisconsin kindred5 (Figure 1; Table S1). Members of the defining family included 13 affected males who presented with variable degrees of ID and early-onset parkinsonism. Multipoint linkage analysis of the Wisconsin family previously localized the disease-causing mutation to Xq27.3–qter with a maximum multipoint LOD of 6.75 at the genetic marker F8C (chrX:154,929,351–154,929,630; GRCh38/hg38).
Wilson_Wisconsin kindred
Family#PresentingHPOs: HP:0001263, HP:0000750, HP:0001249, HP:0002174, HP:0007351, HP:0002362, HP:0002067, HP:0002396, HP:0001260, HP:0000256, HP:0002007, HP:0000218, HP:0001355,
Age at clinical evaluation <2y; early learning difficulty with ability to read and live independently (in some members), age at tremor onset 10-20y, age at Parkinson diagnosis 20s, absent response to L-Dopa, hypokinetic dysarthria, skin depigmented papules, normal cerebellar function and eye examination, normal karyotype, normal copper testing, normal blood count and chemistry, normal urine metabolic testing, normal hearing.
FamilyNotHPOs:
Fragile X syndrome,
CountryOrigin: Germany
Ethnicity:
Race:
Family#PreviousTesting: Multipoint linkage analysis was performed. X chromosome exome sequencing revealed no other variants in the linkage region. Direct sequencing of CLIC2 ruled out variants in the gene.
Family#Method1: Sanger seq
Family#Method2:
Family#GenotypingMethod: RAB39B was directly sequenced
Affected: 16
Unaffected:
Segregations:
PublishedLOD: 6.75
eLOD:
AddSegregationInfo:
ProbandLabel: Wilson_Wisconsin kindred proband
Variant: NM_171998.4(RAB39B):c.503C>A (p.Thr168Lys)
ClinVar: 156532
CAID:
gnomAD: NR
FamilyAddInfo: Family is noted to be of German ancestry, and no consanguinity is noted.
FamilyPMIDs: 1674730, 4025396
The consequences of telomerase deficiency were studied in model organisms before telomerase mutations were discovered in the setting of human disease[18, 19]
Animal Models telomerase deficiency was studied in mouse models prior to their discovery in association with human disease, with dyskeratosis congenita being the first to be associated with TBD
Clinical and genetic characteristics of concomitant Mucopolysaccharidosis type IVA and neurogenic bladder in children: two case reports and literature review
PMID 33407246
Disease Mucopolysaccharidosis IVA
Gene GALNS
Sensory and autonomic deficits in a new humanized mouse model of familial dysautonomia
PMID: 26769677
Gene: ELP1
Disease: Familial dysautonomia
MonDO: MONDO:0009131
InheritancePattern: AR
Notes: Morini_Mouse
Mucopolysaccharidosis IVA: Identification of a Common Missense Mutation I113F in the N-Acetylgalactosamine-6-Sulfate Sulfatase Gene
PMID: 7668283
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes:
RESULTS
NonHumanModel: Murine
GeneAlteration: murine Galns portions of intron 1 and exon 2 were deleted via homologous recombination of a cre-neomycin resistance-cre cassette and mated with a cre recombinase strain to remove the cassette and complete the deletion
ModelPhenotype: No outward phenotypes but biochemically there was up to a 6 fold increase in GAG excretion in urine, chondroitin-6-sulfate specifically and not keratan sulfate, consistent with the human phenotype
HumanPhenotype: in severe cases there are obvious skeletal deformations, increase of GAG's chondroitin-6-sulfate and keratan sulfate in urine and decreased or absent GALNS activity
ModelEvidence: X-rays of mice and multiple life stages, GAG assays in urine, immunohistochemistry images of tissues with labeled chondoritin-6-sulfate and keratan sulfate to show distribution in multiple tissue types and
ModelVariant: large deletion of portion of intron 1 and exon 2
WhereInPaper:
Genetics of human telomere biology disorders
PMID 36151328
Gene TERC
Diseases dyskeratosis congenita, pulmonary fibrosis, Høyeraal–Hreidarsson syndrome, Coats plus syndrome and Revesz syndrome
This is substantiated by the observation that, similarly to some types of SGR that affect the RNA decay machinery (for example, DIS3 or MTREX; Fig. 4c) and likely increase the level of functional hTR, an inhibitor of the hTR poly(A) polymerase PAPD5 increases the level of mature hTR and improves the potential of haematopoietic stem and progenitor cells in the context of PARN or dyskerin deficiency59,237,238,239.
potential gene therapy targets to increase TERC (hTR)
Since then, 16 additional TBD-causing genes have been identified (Table 1)
Important Table of 16 known telomere biology disorder linked genes with synopses of associated diseases and case counts
Short telomeres are a risk factor for idiopathic pulmonary fibrosis
PMID 18753630
Disease pulmonary fibrosis
Mucopolysaccharidosis IVA and glycosaminoglycans
PMID: 27979613
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes: Review
Glycosaminoglycans: KS and C6S
ExperimentName: Accumulation of glycosaminoglycans
GOterm:
FunctionalEvidence: Patient cells assayed with artificial substrates for the N-acetylgalactosamine-6-sulfate sulfatase encoded by GALNS, depending on the severity of the coding sequence alteration, are either unable to break down the substrate or are hindered. Further, in mucopolysaccharidosis IVA patients with known variants, elevated levels of keratan sulfate and chondroitin-6-sulfate can be found in their urine where levels in unaffected individuals are much lower.
HGNC:
GeneEvidence:
SharedGeneImplication:
Molecular analysis of the PAX6 gene in Mexican patients with congenital aniridia: report of four novel mutations
PMID: 18776953
Gene: PAX6
Variant c.-129+9G>A
Disease: Ocular dysgenesis
MonDO: MONDO:0700246
InheritancePattern: AD
A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient
PMID: 19607881
Variant NM_001368894.2:c.136C>G(p.Leu46Val)
Gene: PAX6
Disease: Ocular dysgenesis
InheritancePattern: AD
A novel deletion (IVS11+3del4) identified in the human PAX6 gene in a patient with aniridia
PMID:
Gene: PAX6
Variant NM_000280.5:c.333C>A(p.Val111=)
Disease: Ocular dysgenesis
InheritancePattern: AD
Notes In Table 1. and Figure 3 there are nice illustrations of the consequences of this variant leading to a 27bp truncation in exon 6, in frame, which causes an AA deletion p.Cys112_Val120del version of PAX6. No patient phenotype data is available.
Four patients (2 males, 2 females)
Case#: Fateen_P4
Demographics: Egyptian
CasePresentingHPOs: HP:0000768, HP:0000943, HP:0002857, HP:0000256, HP:0002808, HP:0001382, HP:0005072, HP:0009769 prominent proximal metaphyses
CaseNotHPOs:
CasePreviousTesting:
CaseMethod1:
CaseMethod2:
CaseGenotypingMethod: single gene seq by Sanger of all 14 exons and restriction digest confirmation/ screening of parents and controls
Variant: NM_000512.5(GALNS):c.119A>G (p.Asp40Gly)
ClinVar: 1048369
CAID: CA397100962
gnomAD: n/a
VariantEvidence: hydrophillic>hydrophobic substitution in putative active site and enzyme activity data shows low enzyme function compared to reference range
CaseAddInfo:
CasePMIDs:
Exome Sequencing Identifies a Biallelic GALNS Variant (p.Asp233Asn) Causing Mucopolysaccharidosis Type IVA in a Pakistani Consanguineous Family
PMID: 36292628
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes: Case report
The clinical and functional effects of TERT variants in myelodysplastic syndrome
PMID 34019641
Phenotypes HP:0031413, HP:0002863
Phenotypes free-text short telomere length, myelodysplastic syndrome
Mutation profiles and clinical characteristics of Chinese males with isolated hypogonadotropic hypogonadism
PMID 30098700
PMID: 9536098
Gene: PAX6
Variant NM_001368894.2:c.-128-2del
Disease: Ocular dysgenesis
InheritancePattern: AD
Disease PAX6-related ocular dysgenesis MONDO:0800183
Lost in translation: returning germline genetic results in genome-scale cancer research
PMID: 28454591
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germline mutations and genotype–phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea J.H. Kim, J.H. Kim Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaBoth the authors contributed equally to this work.Search for more papers by this authorM.-W. Seong, M.-W. Seong Department of Laboratory medicine, Seoul National University College of Medicine, Seoul, South KoreaBoth the authors contributed equally to this work.Search for more papers by this authorK.E. Lee, K.E. Lee Department of Surgery, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorH.J. Choi, H.J. Choi Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South KoreaSearch for more papers by this authorE.J. Ku, E.J. Ku Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorJ.H. Bae, J.H. Bae Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.S. Park, S.S. Park Department of Laboratory medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.H. Choi, S.H. Choi Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.W. Kim, S.W. Kim Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorCS Shin, CS Shin Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.Y. Kim, Corresponding Author S.Y. Kim Department of Internal medicine, Seoul National University College of Medicine, Seoul, South Korea Corresponding author: Prof Seong Yeon Kim, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 110-744, South Korea. Tel.: 082-02-2072-3216; fax: 082-02-762-9662; e-mail: seongyk@plaza.snu.ac.krSearch for more papers by this author
PMID: 24134185
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Sequence Variations in the von Hippel–Lindau Tumor Suppressor Gene in Patients with Intracranial Aneurysms
PMID: 23434161
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Outcome and genetic analysis of patients affected by retinal capillary hemangioblastoma in von Hippel Lindau syndrome
PMID: 34566400
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan
PMID: 8956040
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
A case of 3p deletion syndrome associated with cerebellar hemangioblastoma
PMID: 26365017
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Associations between VHL genotype and clinical phenotype in familial von Hippel-Lindau disease
PMID: 17537157
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Mutation screening of VHL gene in a family with malignant bilateral pheochromocytoma: from isolated familial pheochromocytoma to von Hippel-Lindau disease
PMID: 19649731
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Pheo-Type: A Diagnostic Gene-expression Assay for the Classification of Pheochromocytoma and Paraganglioma
PMID: 26796762
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Von Hippel Lindau Disease
PMID: 30853203
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Clear cell chondrosarcoma in Von Hippel-Lindau disease
PMID: 31673890
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Three novel VHL germline mutations in Korean patients with von Hippel-Lindau disease and pheochromocytomas
PMID: 16142346
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene
PMID: 8550742
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Mutation of the Von Hippel-Lindau tumour suppressor gene in capillary haemangioblastomas of the central nervous system
PMID: 8758206
Gene: VHL
StandardizedReferenceSequence: NM_000551.3