[Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology]
PMID: 35395997
InsufficientEvidence: Article in Chinese, and variant reported doesn't have a corresponding shift reported in humans.
Mr P ..., 67 years
Case1: Male, 67 years old, ethnicity not specified (although lives in Argentina)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo:
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000978, HP:0100749 (Bruising, chest pain)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: Platelets fail to aggregate and bind to fibrinogen in response to ADP, collagen and thrombin
CasePreviousTesting: N/A
Gene: ITGB3
Variant: NM_000212.2:c.2332T>C (p.Ser778Pro)
LegacyVariant: (p.Ser752Pro)
ClinVar: 13556
CAiD: CA123230
gnomAD: N/A
Supplemental Table S1:
Case24: N/A (from Turkey)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: Individual clinical data not given
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: <5% αIIbβ3 expression
PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
Gene: ITGA2B
Variant: Thr646Ala* (Need to consult senior biocurator to figure this variant out) will note it as Unknown as I am not sure of it
LegacyVariant: ^
ClinVar: ^
CAiD: ^
gnomAD: ^
PreviouslyPublished: PMID: 25734216
Supplemental Table S1:
Case34: Female, Germany, age not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Moderate to severe bleeding that prompted transfusion
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: <5% αIIbβ3 expression
PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
Gene: ITGA2B
Variant: (p.Cys705Leu) not getting this to show up in CAR need to consult senior biocurator noting this as Unknown Variant --> Variant can't be identified
LegacyVariant: N/A
ClinVar: N/A
CAiD: ^
gnomAD: ^
PreviouslyPublished: PMID: 20345392
3
Case3: Male, Iraq, age not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper
ParentalGenotype: N/A
CasePresentingHPOs: HP:0030137, HP:0000421, HP:0000225, HP:0031364, HP:0002249
(Prolonged bleeding following circumcision, epistaxis, ecchymosis, melena)
CaseHPOFreeText: Haematemesis
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
CasePreviousTesting: N/A
Gene: ITGB3
Variant: HGVS nomenclature not available. p.Val721Cysfs*33
LegacyVariant: p.Val695Cysfs*33
ClinVar: 13563
CAiD: N/A
gnomAD: N/A
2:20-3:30
How I manage pregnancy in women with Glanzmann thrombasthenia
PMID: 35286390
Gene: ITGA2B, ITGB3
GNC: 6138, 6156
GT7
Case: 20 year old female French Gypsy
CasePresentingHPOs: HP:0001975
(Decreased platelet glycoprotein IIb-IIIa)
GenotypingMethod:Genotyping analysis of the HPA-1 system by high resolution melting analysis (methods not provided, cited article I don't have access too)
not highly specific mutation: "p.Gln228/p.Arg584"
Allele1
ClinVar: Not found
CAID: PA913203366
Variant: NP_000410.2:p.Gln228Ter
GnomAD: not found
Allele 2
ClinVar: Not found
CAID: PA115836
Variant: NP_000410.2:p.Arg584Ter
GnomAD: Not found
ExpressionEvidence: "Severe defective surface expression" of platelet surface αIIbβ3 integrin (methods not provided cited article no access too)
GT 20
Case22: GT20, Female, India, age of onset is 25 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation
CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene
Gene: ITGB3
Variant: NM_000212.2:c.2186_2187insT (p.Ile730His), NM_000212.2:c.2191_2192delinsG (p.Leu731Gly), NM_000212.2:c.2201_2206del (p.743Gly_735Iledel)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940729, CA915940730, CA915940731
gnomAD: N/A
Supplementary Table S1 & S2 Proband and Variant Information:
Case25: GT28, Male, 36, French/Syrian
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Affected sister (See Supplemental Table 1)
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed 5-10% expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: "LR Dup" (See Supplementary Table 1)
LegacyVariant: N/A
ClinVar: N/A
CAiD: N/A
gnomAD: N/A
GT11
Case29: (GT11) Gender, age and ethnicity are not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
CaseNotHPOs: N/A
ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
Gene: ITGB3
Variant: NM_000212.2:c.2217del
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940690
gnomAD N/A
GT3
Case18: (GT3) Gender, age and ethnicity are not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Has one brother and sister without the mutation and has one brother that is heterozygous for the variant
ParentalGenotype: Mother and father are both heterozygous for the mutation
CasePresentingHPOs: N/A
CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
CaseNotHPOs: N/A
ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
Gene: ITGB3
Variant: NM_000212.2:c.2315T>C (p.Leu772Pro)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA400034691
gnomAD MAF in the African population is 0.00006152 https://gnomad.broadinstitute.org/variant/17-45387518-T-C
GT-22c
Case20: (GT-22) Female, age or ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Proband GT-22 is related to GT-21 see Table 1
ParentalGenotype: Parents may be included in Table 1; however, not specified so no information
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding severity: Severe (See Supplementary Table 3)
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)
PlateletAggregation: Minimal information (See Supplementary Table 3)
CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.
Gene: ITGB3
Variant: NM_000212.2:c.2302-1G>A
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA400034626
gnomAD: N/A
GT-13
Case13: GT-13, gender, age, ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: Segregation analysis confirmed the presence of heterozygous mutations in carrier parents
CasePresentingHPOs: N/A
CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed <5% of αIIbβ3 expression
PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.
CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples
Gene: ITGA2B
Variant: (p.Trp51Ter)
LegacyVariant: N/A
ClinVar: N/A
CAiD: Unregistered Variant
gnomAD: N/A
A Three Amino Acid Deletion in Glycoprotein IIIa Is Responsible for Type I Glanzmann's Thrombasthenia: Importance of Residues Ile325Pro326Gly327 for β3 Integrin Subunit Association
PMID: 9226167
Gene: ITGB3
VON HIPPEL-LINDAU SYNDROME PRESENTING AS PHEOCHROMOCYTOMA COMPLICATED WITH MYOCARDIAL INFARCTION: A CASE REPORT
PMID: N/A - No PMID
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Locate: Abstract can be found at: https://journals.lww.com/jhypertension/Abstract/2021/04001/VON_HIPPEL_LINDAU_SYNDROME_PRESENTING_AS.761.aspx
Cite: Yu, Huizhen, Lin, Lichao, Yu, Peng, Chen, Qing, Deng, Chaochao. Von Hippel-Lindau Syndrome Presenting as Pheochromocytoma Complicated with Myocardial Infarction: A Case Report. Journal of Hypertension: April 2021 - Volume 39 - Issue - p258 doi: 10.1097/01.hjh.0000747400.32772.50
Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene
PMID: 28849724 Gene: VHL StandardizedReferenceSequence: NM_000551.3
PARS PLANA VITRECTOMY IN ADVANCED CASES OF VON HIPPEL–LINDAU EYE DISEASE
PMID: 26308528
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germ-line mutation analysis in patients with von Hippel-Lindau disease in Japan: an extended study of 77 families
PMID: 10761708
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Pancreatic involvement in von Hippel-Lindau disease: report of two cases and review of the literature
PMID: 16952288
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
More than It Meets the Eye! Vision Loss as a Presenting Symptom of von Hippel-Lindau Disease
PMID: 33531956
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Molecular genetic diagnosis of von Hippel-Lindau disease in familial phaeochromocytoma.
PMID: 8592333
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Von Hippel-Lindau with early onset of hemangioblastoma and multiple drop-metastases like spinal lesions
PMID: 30278534
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Genetics of pheochromocytoma and paraganglioma in Spanish pediatric patients
PMID: 23404858
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Synonymous but Not Silent: A Synonymous VHL Variant in Exon 2 Confers Susceptibility to Familial Pheochromocytoma and von Hippel-Lindau Disease
PMID: 30946460
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Genotype-phenotype correlation in von Hippel-Lindau disease: identification of a mutation associated with VHL type 2A
PMID: 8863170
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Somatic mutations in VHL germline deletion kindred correlate with mild phenotype
PMID: 14755727
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
MODERATED POSTER SESSION - 4: MP4-01: VHL with adrenal pheochromocytoma needs multidisciplinary approach – a case report
PMID: N/A
OVID: 620924735
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germline mutations of the VHL gene in seven Chinese families with von Hippel-Lindau disease
PMID: 21972040
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Bilateral papillopathy as a presenting sign of pheochromocytoma associated with von Hippel–Lindau disease
PMID: 24707167
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Systematic genetic screening in a prospective group of Danish patients with pheochromocytoma
PMID: 28721348
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene are similar to somatic von Hippel-Lindau aberrations in sporadic renal cell carcinoma
PMID: 7977367
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Metastatic phaeochromocytoma in a 23-year-old woman with an unclassified variant in the von Hippel Lindau disease gene: how can the pathogenicity of this variant be determined? Nicholas Russell, Corresponding Author Nicholas Russell Department of Endocrinology, Austin Health, Heidelberg, VIC, AustraliaCorrespondence: Nicholas Russell, nicholas.russell@austin.org.auSearch for more papers by this authorMartin Delatycki, Martin Delatycki Department of Medicine Austin Health, University of Melbourne, Heidelberg, VIC, Australia Clinical Genetics Service, Austin Health, Heidelberg, VIC, AustraliaSearch for more papers by this authorMathis Grossmann, Mathis Grossmann Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia Department of Medicine Austin Health, University of Melbourne, Heidelberg, VIC, Australia Clinical Genetics Service, Austin Health, Heidelberg, VIC, AustraliaSearch for more papers by this author
PMID: 25557216
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
A deletion mutation of the VHL gene associated with a patient with sporadic von Hippel-Lindau disease
PMID: 23632291
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Clinical and molecular characterization of Brazilian families with von Hippel-Lindau disease: a need for delineating genotype-phenotype correlation
PMID: 20567917
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Endocrine Manifestations of Von Hippel–Landau Disease
PMID: 31016171
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity
PMID: 22103590
Gene: F9
HGNC: 3551
Fluorinated low-viscosity copolymer with enhanced release property for roll-to-plate UV nanoimprint lithography
PMID: 31480035
Gene: F8
NoEvidence: No mention of blood disorders, Hemophilia or F8 here. Search engine might have seen EP-F8, which is a compound oxirane-- not the F8 gene.
PMID: 8320491
Gene: F9
HGNC: 3551
ssODN-Mediated In-Frame Deletion with CRISPR/Cas9 Restores FVIII Function in Hemophilia A-Patient-Derived iPSCs and ECs
PMID: 31261034
Gene: F8
Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A
PMID: 31236667
Gene: F8
Novel approach to genetic analysis and results in 3000 hemophilia patientsenrolled in the My Life, Our Future initiative
PMID: 29296726
Gene: F9
HGNC: 3551
PMID: 25251685
Gene: F9
HGNC: 3551
Consequences of factor IX mutations in 26 families with haemophilia B
PMID: 9450791
Gene: F9
HGNC: 3551
Analysis of the N-glycans of recombinant human Factor IX purified from transgenic pig milk
PMID: 18456721
Gene: F9
HGNC: 3551
The Arg-4 mutant factor IX Strasbourg 2 shows a delayed activation by factor XIa
PMID: 8295821
Gene: F9
HGNC: 3551
Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as "spacer" elements
PMID: 1680287
Gene: F9
HGNC: 3551
Enhanced potency of recombinant factor VIIa with increased affinity to activated platelets
PMID: 31549480
Gene: F8
InsufficientEvidence: This article mentions variants and patient tissue being used separately; however, does not tie them in together, without a variant to tie the proband to, it’s insufficient evidence.
FIX mutation spectrum in haemophilia B patients from Jordan: identification of three novel mutations
PMID: 20695909
Gene: F9
HGNC: 3551
Monitoring once-weekly recombinant factor IX prophylaxis in hemophilia B with thrombin generation assay and factor IX activity V. Nummi, V. Nummi orcid.org/0000-0002-5134-7288 Faculty of Medicine, University of Helsinki, Helsinki, Finland Coagulation Disorders Unit, Department of Hematology and Comprehensive Cancer Center, Laboratory Services, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorA. Jouppila, A. Jouppila Helsinki University Hospital Research Institute, Helsinki, FinlandSearch for more papers by this authorR. Lassila, Corresponding Author R. Lassila riitta.lassila@hus.fi Faculty of Medicine, University of Helsinki, Helsinki, Finland Coagulation Disorders Unit, Department of Hematology and Comprehensive Cancer Center, Laboratory Services, Helsinki University Hospital, Helsinki, Finland Correspondence: Riitta Lassila, Coagulation Disorders Unit, Department of Hematology and Comprehensive Cancer Center, Laboratory Services, Helsinki University Hospital, P.O. Box 372, 00029 HUS, Helsinki, Finland. Tel.: +358 40 517 5547; Fax: +358 9 471 74504; E-mail: riitta.lassila@hus.fiSearch for more papers by this author
PMID: 28406575
Gene: F9
HGNC: 3551
Clinical Problem Solving and Using New Paths in the Laboratory: Learning from Case Studies
PMID: 32820490
Gene: F9
HGNC: 3551
Factor IX mutations in Haemophilia B patients in Malaysia: a preliminary study
PMID: 22870602
Gene: F9
HGNC: 3551
Glucose hypometabolism in the visual cortex proportional to disease severity in patients with essential blepharospasm.
PMID: 31487599
Gene: F8
NoEvidence: No mention of blood disorders, F8 or Hemophilia A in this article.
Characterization of genetic defects of hemophilia B of Chinese origin
PMID: 1796396
Gene: F9
HGNC: 3551
The CDC Hemophilia B mutation project mutation list: a new online resource
PMID: 24498619
Gene: F9
HGNC: 3551
Usual and unusual mutations in a cohort ofBelgian patients with hemophilia B
PMID: 27865967
Gene: F9
HGNC: 3551
Predictive Value of Slow and Fast EEG Oscillations for Methylphenidate Response in ADHD
PMID: 31304784
Gene: F8
NoEvidence: This article is not about Hemophilia A, blood disorders, or F8. This article is centered around ADHD.
Mutations of 60 known causative genes in 157 families with retinitis pigmentosa based on exome sequencing
PMID: 24938718
Gene: TOPORS
1
Case#: Subject 1, female, in her 30s (age at enrollment), died during extension study from pneumonia and respiratory failure sixty-five days after her first dose in the extension study.
DiseaseAssertion: MPS1-HS
FamilyInfo: N/A
CasePresentingHPOs: HP:0002093, HP:0002540, HP:0002090, HP:0002176 (Chronic respiratory insufficiency, inability to walk, pneumonia, spinal cord compression)
CaseHPOFreeText: Hemidiaphragmatic paralysis, improved strength and range of motion
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes - Enzyme replacement therapy with laronidase
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
Genetic testing of Mucopolysaccharidoses disease using multiplex PCR- based panels of STR markers: in silico analysis of novel mutations
PMID: 31236806
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Nationwide Newborn Screening Program for Mucopolysaccharidoses in Taiwan and an Update of the “Gold Standard” Criteria Required to Make a Confirmatory Diagnosis
PMID: 34573925
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
6
Case#: 6, Male, 0.9 years (diagnosed), 13.0 years (report), 15 kg (weight), 102 cm (height), Iranian
DiseaseAssertion: Hurler Syndrome
FamilyInfo: Parents are consanguineous
CasePresentingHPOs: HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0100790, HP:0000365, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia, Deafness, Hydrocephalus)
CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea
CaseNotHPOs: HP:0007957 (Corneal Capacity)
CaseNotHPOFreeText: Cardiac Manifestations
CaseEnzymeAssay: IDUA activity 1.3 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 11.54 (mg/gCr)
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sanger Sequencing
Variant1: p.D301E
Variant2: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
13
Case#: 13, Male, 0.8 years (diagnosed), 1.6 years (report), 7.2 kg (weight), 71 cm (height), Iranian
DiseaseAssertion: Scheie Syndrome
FamilyInfo: Parents are not consanguineous
CasePresentingHPOs: HP:0001249, HP:0001999, HP:0100790 (Mental Retardation, Facial Dysmorphic Features, Hernia)
CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea
CaseNotHPOs: HP:0000943, HP:0001387, HP:0000365, HP:0007957, HP:0000238 (Multiple Dysostosis, Joint Stiffness, Deafness, Corneal Opacity, Hydrocephalus)
CaseNotHPOFreeText: Cardiac Manifestations
CaseEnzymeAssay: IDUA activity 0.75 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 7.4 (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
21
Case#: 21, Female, 0.8 years (diagnosed), 2.8 years (report), 7.5 kg (weight), 80 cm (height), Iranian
DiseaseAssertion: Hurler Syndrome
FamilyInfo: Parents are consanguineous
CasePresentingHPOs:HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0100790, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia, Deafness, Corneal Capacity, Hydrocephalus)
CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea, Cardiac Manifestations (mitral stenosis)
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA activity 0.98 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 10.5 (mg/gCr)
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sanger Sequencing
Variant1: Not Provided
Variant2: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
7
Case#: 7, Female, 0.7 years (diagnosed), 12.9 years (report), 14.2 kg (weight), 97 cm (height), Iranian
DiseaseAssertion: Hurler-Scheie Syndrome
FamilyInfo: Parents are consanguineous
CasePresentingHPOs: HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0100790, HP:0000365, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia, Deafness, Hydrocephalus)
CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea
CaseNotHPOs: HP:0007957 (Corneal Capacity)
CaseNotHPOFreeText: Cardiac Manifestations
CaseEnzymeAssay: IDUA activity 0.86 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 10.11 (mg/gCr)
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sanger Sequencing
Variant1: p.G84R
Variant2: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
8
Case#: 8, Female, 0.7 years (diagnosed), 1.3 years (report), 7.0 kg (weight), 70 cm (height), Iranian
DiseaseAssertion: Hurler-Scheie Syndrome
FamilyInfo: Parents are consanguineous
CasePresentingHPOs: HP:0100790 (Hernia)
CaseHPOFreeText: 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: HM/HSM, Cardiac Manifestations
CaseEnzymeAssay: IDUA activity 1.06 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 6.7 (mg/gCr)
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sanger Sequencing
Variant1: p.G84R
Variant2: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
3
Case#: 3, Male, 0.2 years (diagnosed), 1.5 years (report), 7.5 kg (weight), 72 cm (height), Iranian
DiseaseAssertion: Hurler-Scheie Syndrome
FamilyInfo: Parents are consanguineous
CasePresentingHPOs: N/A
CaseHPOFreeText: Chronic Rhinorrhea
CaseNotHPOs: HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0100790, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia, Deafness, Corneal Opacity, Hydrocephalus)
CaseNotHPOFreeText: HM/HSM, Cardiac Manifestations
CaseEnzymeAssay: IDUA activity 0.76 (μmol/spot.20h)
CaseUrineGAGs: Quantitative urinary GAG 10.80 (mg/gCr)
CaseERT: N/A
CaseBMT: N/A
GenotypingMethod: Sanger Sequencing
Variant1: p.Y109H
Variant2: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
12 year follow up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I: the important role of early treatment
PMID: 26965916
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
older sibling
Case#: OS of sibship 8, male, 6.8 years old (age at diagnosis), 7 years old (age at ERT enrollment), 6.0 years (duration of ERT)
DiseaseAssertion: MPS1-HS
FamilyInfo: Affected YS (YS of sibship 8)
CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contracture)
CaseHPOFreeText: Cardiac disease
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes - Had progression of cardiac symptoms at T2 and dysostosis multiplex stabilized. Had behavioral issues and required an aide for 1-on-1 schooling.
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
younger sibling
Case#: YS of sibship 9, female, 6.7 years old (age at diagnosis), 8.6 years old (age at ERT enrollment), 6.4 years (duration of ERT)
DiseaseAssertion: MPS1-HS
FamilyInfo: Affected OS (OS 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 - Had stabilization of mild ocular symptoms, and cardiac disease remained less severe in the mild to moderate range. 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
the youngest
Case#: YS of sibship 6 (see Table 1), male, 0.6 years old (age at diagnosis), 3 years old (age at ERT enrollment), 7 years (duration of ERT)
DiseaseAssertion: MPS-HS
FamilyInfo: Two affected siblings (OS1 and OS2 of sibship 6)
CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contractures)
CaseHPOFreeText: Cardiac disease, musculoskeletal symptoms
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes - Pulmonary function was 70–80 % of normal and had no restrictions in ADL.
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
Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships
PMID: 26446585
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
younger sibling
Case#: YS of sibship 3, female, 0.4 years old (age at diagnosis), 0.7 years old (age at ERT enrollment), 8.3 years (duration of ERT)
DiseaseAssertion: MPS1-HS
FamilyInfo: Affected female OS (OS of sibship 3)
CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contractures)
CaseHPOFreeText: Cardiac disease, mild musculoskeletal symptoms, mild to moderate ocular disease.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: Yes - After 8 years of ERT had no restrictions in ADL, no cognitive delays, and only mild musculoskeletal symptoms and mild to moderate ocular disease and cardiac symptoms remained stable.
CaseBMT: N/A
Variant1: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Neurocognitive and somatic stabilization inpediatric patients with severeMucopolysaccharidosis Type I
PMID: 29976218 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive
c.1898C>G/p.Ser633Trp Mutation in Alpha-l-Iduronidase: Clinical and Structural Implications
PMID: 33389473
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
PMID: 8328452
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
D1
Case#: Patient D1, Druze religious group, located in lower Galilee.
DiseaseAssertion: MPS1-H
FamilyInfo: Both parents, as well as an aunt and uncle who had a deceased affected child, were heterozygous for the same mutation.
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.192C>A (p.Y64X)
Variant1ClinVarID: 11914
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
c.235G>A
Case#: Functional assay variant with a clinical significance of clinically benign.
DiseaseAssertion: MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.235G>A (p.A79T)
Variant1ClinVarID: 195038
Variant1CAID: CA201508
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
c.298A>G
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.298A>G (p.R100G)
Variant1ClinVarID: 2058952
Variant1CAID: CA2801159
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
24/M
Case#: Patient 24, male, Han origin, age not available
DiseaseAssertion: N/A
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA activity 2.3 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: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: c.296+4G>A, it looks like this is a typo and should be c.299+4G>A
Variant2ClinVarID: N/A
Variant2CAID: CA2669476183
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
An algorithm to predict phenotypic severity in mucopolysaccharidosis type I in the first month of life
PMID: 23837464
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Rapid and accurate denaturating high performance liquid chromatography protocol for the detection of alpha-l-iduronidase mutations causing mucopolysaccharidosis type I
PMID: 19954743
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
A novel compound mutation in alpha-L-iduronidase gene causes mucopolysaccharidosis type I
PMID: 31544795
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Case#: CA-106 ID number, Table S1.1 of Supplementary Material. Male, 5 months old (age at first symptoms), 6.5 months old (age at diagnosis). Stored frozen (-20ºC) 1.3 yr
DiseaseAssertion: Severe MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Bump on back, chronic breathing problems, moderate-severe hearing loss.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: 1351 fmol/punch
CaseERT: N/A
CaseBMT: Yes - In April 2018
Variant1: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Case#: NY-604 ID number, Table S1.1 of Supplementary Material. Additional health information not provided.
DiseaseAssertion: Severe MPS-I
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: 2315 fmol/punch
CaseERT: N/A
CaseBMT: N/A
Variant1: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Case#: NJ-501 ID number, Table S1.1 of Supplementary Material. Male, 1 year and 1 month (age at first symptoms), 1 year and 2 months old (age at diagnosis). Stored ambient 3 yr
DiseaseAssertion: Severe MPS-I
FamilyInfo: N/A
CasePresentingHPOs: Macrocephaly, kyphosis, coarse facial features, corneal clouding, hearing impairment, developmental delays, speech delays (HP:0000256, HP:0002808, HP:0000280, HP:0007957, HP:0000365, HP:0001263, HP:0000750)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: 1147 fmol/punch
CaseERT: N/A
CaseBMT: N/A
Variant1: N/A
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Mucopolysaccharidosis type I in 21 Czech and Slovak patients: Mutation analysis suggests a functional importance of C-terminus of the IDUA protein
PMID: 19396826
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Mucopolysaccharidosis type I newborn screening: Importance of second tier testing for ethnically diverse populations Kerri Bosfield, Kerri Bosfield orcid.org/0000-0001-5135-3779 Children's National Hospital, Washington, DC, USASearch for more papers by this authorDebra S. Regier, Corresponding Author Debra S. Regier dregier@childrensnational.org orcid.org/0000-0001-7525-0088 Children's National Hospital, Washington, DC, USA Correspondence Debra S. Regier, Children's National Hospital, 111 Michigan Ave NW, Washington, DC 20010, USA. Email: dregier@childrensnational.orgSearch for more papers by this authorSarah Viall, Sarah Viall Children's National Hospital, Washington, DC, USASearch for more papers by this authorRebecca Hicks, Rebecca Hicks Children's National Hospital, Washington, DC, USASearch for more papers by this authorNatasha Shur, Natasha Shur orcid.org/0000-0003-1336-747X Children's National Hospital, Washington, DC, USASearch for more papers by this authorChristina L. Grant, Christina L. Grant Children's National Hospital, Washington, DC, USASearch for more papers by this author
PMID: 33098355
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Mutation analysis and clinical characterization of Iranianpatients with mucopolysaccharidosis type I
PMID: 31386236 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive
Hurler disease
Case#: Patient 49, 2 years old (age at report), male, Indian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002719, HP:0000943, HP:0100790)
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.(1189+1)(1190–1)(1959_?)del in the paper, unsure how to write this in current nomenclature.
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: c.(1189+1_1190-1)(2003?)del in the paper, unsure how to write this in current nomenclature.
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Hurler disease
Case#: Patient 47, 2 years old (age at report), female, Indian
DiseaseAssertion: MPS1-H
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: 1.8% (Range of residual enzyme activity: 0.0%-4.8%)
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: N/A
Variant1: c.(792+1_793-1)_(972+1_973-1)del in the paper, unsure how to write this in current nomenclature.
Variant1ClinVarID: N/A
Variant1CAID: N/A
Variant2: c.(792+1_793-1)_(972+1_973-1)del in the paper, unsure how to write this in current nomenclature.
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Effect of small molecule eRF3 degraders on premature termination codon readthrough
PMID: 33764477
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
18-year follow-up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I
PMID: 36333985
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients
PMID:35614200
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
A list of 11 IDUA variants identified in cases with MPS is included in Supplemental Table 6, but the variants are not linked to specific patients and are listed individually (not as genotypes). A page note has been added for each variant.
Unrelated CD3/CD19-depleted peripheral stem cell transplantation for Hurler syndrome
PMID: 25116402
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Whole paternal uniparental disomy of chromosome 4 with a novel homozygous IDUA splicing variant, c.159‐9T>A, in a Chinese patient with mucopolysaccharidosis type I
PMID: 39132856
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Differences in MPS I and MPS II Disease Manifestations
PMID: 34360653
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Identification of a novel compound heterozygous IDUA mutation underlies Mucopolysaccharidoses type I in a Chinese pedigree
PMID: 31758674
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Mutation c.1190-1delG/N in intron 8 and c.1708G>C/N in exon 12 not reported in the IDUA gene developed a clinical phenotype of Scheie syndrome
PMID: 25558755
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
III-3,
Case: Patient III-3 (proband's granduncle; father of IV-2 and IV-3) DiseaseAssertion: Type 2A VWD, based on low plasma VWF:Ag and activity and lack of plasma HMW VWF multimers (diagnosis explicitly extended to this patient along with proband and IV-2, IV-3, IV-4). FamilyInfo: Granduncle of proband V-2; father of IV-2 and IV-3 (both also affected); part of 5-affected-member pedigree (Fig. 1). ParentalGenotype(s): NA — his own parents' (generation II) genotype status not reported. CasePresentingHPOs: HP:0012147 (Reduced quantity of VWF; VWF:Ag 21.6 U/dL), HP:0030129 (Impaired VWF:RCo; VWF:Rco 5.0 U/dL), HP:0030132 (Absence of large VWF multimers — plasma), HP:0003645 (Prolonged partial thromboplastin time; APTT 45.5 sec) CaseHPOFreeText: Described only generically as having "abnormal bleedings" / "similar clinical symptoms" to the proband — no itemized bleeding symptoms given for this individual specifically. FVIII:C 28.0 U/dL (nv 50-150). RIPA not tested (N/A). TT 16.7 sec and PT 14.0 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
The proband was a 9-year-old boy, whose family pedigree is shown in Fig. 1. He suffered from frequent bruise, epistaxis, prolonged bleedings from small wounds, and delayed wound healing.
Case: Patient V-2, Male, 9 years old (proband) DiseaseAssertion: Type 2A VWD, based on history of abnormal bleeding, low plasma VWF:Ag and activity, low FVIII:C, and lack of plasma HMW VWF multimers. FamilyInfo: Proband of a pedigree (Fig. 1) with 5 affected individuals (V-2, III-3, IV-2, IV-3, IV-4) across multiple generations, all carrying the same variant; unaffected father (IV-5) does not carry it. ParentalGenotype(s): Mother (IV-4) heterozygous for the variant, affected. Father (IV-5) does not carry the variant, unaffected (normal VWF:Ag 95.2 IU/dL, normal multimer pattern). CasePresentingHPOs: HP:0000421 (Epistaxis), HP:0001934 (Persistent bleeding after trauma — "prolonged bleedings from small wounds"), HP:0012147 (Reduced quantity of VWF; VWF:Ag 20.5 U/dL), HP:0030129 (Impaired VWF:RCo; VWF:Rco 6.2 U/dL), HP:0030132 (Absence of large VWF multimers — plasma), HP:0011871 (Impaired RIPA; 28.5%), HP:0003645 (Prolonged partial thromboplastin time; APTT 58.1 sec) CaseHPOFreeText: Frequent bruising, delayed wound healing (no matching HPO code in the approved list); FVIII:C 25.0 U/dL (nv 50-150); TT 16.7 sec and PT 14.2 sec both within normal range. CaseNOTHPOs: NA CaseNOTHPOFreeText: Platelet-associated VWF multimers were normal (HMW multimers present, indistinguishable from controls) despite the plasma multimer defect — supports a secretion defect rather than a synthesis defect. CasePreviousTesting: Not genome-wide; targeted VWF gene analysis — Sanger sequencing of all 52 exons and intron-exon boundaries of VWF using published primers, followed by allele-specific cloning (pMD18-T vector) and sequencing to resolve the heterozygous deletion. GenotypingMethod: Direct Sanger sequencing (Applied Biosystems 310 DNA analyzer) of all VWF exons/boundaries; PCR amplification and cloning of individual alleles into pMD18-T vector to confirm and characterize the heterozygous deletion. PreviouslyPublished: NA — first report of this variant/family. Gene: VWF Variant: Novel heterozygous in-frame 6-bp deletion in exon 28, removing residues D1529 and V1530 (ΔD1529V1530) in the VWF A2 domain. Functional studies (HEK293 transfection) showed the mutant is expressed but its secretion is markedly impaired (42±4% of WT in conditioned medium, p<0.01) with intracellular retention (174±29% of WT in cell lysate, p<0.05) and ER colocalization (PDI co-staining); co-transfection with WT VWF reduced WT secretion (61±16% of WT alone, p<0.05), indicating a dominant-negative effect. Classified as a "Group I" type 2A mechanism (impaired intracellular transport/secretion). HGVS: c.4585_4590del (p.Asp1529_Val1530del) — confirmed against the authors' GenBank submission (JN625247) and cross-validated against a real ClinVar-confirmed exon 28 variant ClinVarID: NA CAID: NA gnomAD: NA
von Willebrand disease
Gene: VWF
PMID: 9299039
6
Case: Patient 6 (Family B), male, 15yo
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 A, Platelet count x103/μl = 180, PFA 100 sec = >300, SPA % = 0, MADR mg/mL = 0.6, VWF:Ag U/dL = 30.9, VWF:CB U/dL = 12.5, VWF:CB ratio = 0.41, VWF:RCo U/dL = 11.4, VWF:RCo ratio = 0.37, Platelet VWF U/dL = 79.1, FVIII U/dL = 49.3, BAT F/M = 4
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
1
Case: Patient 1 (Family A), female, 48yo
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 A, Platelet count x103/μl = 232, PFA 100 sec = NA, SPA % = 12, MADR mg/mL = 0.45, VWF:Ag U/dL = 160.6, VWF:CB U/dL = 135.6, VWF:CB ratio = 0.84, VWF:RCo U/dL = 132.8, VWF:RCo ratio = 0.83, Platelet VWF U/dL = 92.0, FVIII U/dL = 78.0, BAT F/M = 6
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: Sequencing of exon 28 of VWF
PreviouslyPublished: NA
Gene: VWF
Variant: c.4115T>G (p.Ile1372Ser)
HGVS: NM_000552.4(VWF):c.4115T>G (p.Ile1372Ser)
ClinVarID: 100327; https://www.ncbi.nlm.nih.gov/clinvar/variation/100327/
gnomAD: MAF = 0.00006175 (7/113356 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128469-A-C?dataset=gnomad_r2_1
11
Case: Patient 11 (Family C), male, 80yo
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 = 182, PFA 100 sec = >300, SPA % = 0, MADR mg/mL = 0.45, VWF:Ag U/dL = 39.5, VWF:CB U/dL = 9.3, VWF:CB ratio = 0.24, VWF:RCo U/dL = 23.3, VWF:RCo ratio = 0.59, Platelet VWF U/dL = 113.90, FVIII U/dL = 52.1, BAT F/M = 14
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
7
Case: Patient 7 (Family B), male, 81yo
DiseaseAssertion: VWD2B
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0030132, HP:0030129, HP:0030130, HP:0011871
(Absence of large von Willebrand factor multimers, impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA)
CaseHPOFreeText: blood group A, Platelet count x103/μl = 165, PFA 100 sec = >300, SPA % = NA, MADR mg/mL = 0.6, VWF:Ag U/dL = 166.4, VWF:CB U/dL = 30.0, VWF:CB ratio = 0.18, VWF:RCo U/dL = 112.0, VWF:RCo ratio = 0.67, Platelet VWF U/dL = NA, FVIII U/dL = 136.0, 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
17
Case: Patient 17 (Family E), female, 24yo
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 = 65, PFA 100 sec = >300, SPA % = 22.5, MADR mg/mL = 0.15, VWF:Ag U/dL = 35.9, VWF:CB U/dL = 15.6, VWF:CB ratio = 0.44, VWF:RCo U/dL = 14.4, VWF:RCo ratio = 0.40, Platelet VWF U/dL = 140.3, FVIII U/dL = 35.9, BAT F/M = 13
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: Sequencing of exon 28 of VWF
PreviouslyPublished: NA
Gene: VWF
Variant: c.3946G>A (p.Val1316Met)
HGVS: NM_000552.4(VWF):c.3946G>A (p.Val1316Met)
ClinVarID: 290; https://www.ncbi.nlm.nih.gov/clinvar/variation/290/
CAID: NA
gnomAD: absent
4
Case: Patient 4 (Family A), male, 43yo
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 A, Platelet count x103/μl = 163, PFA 100 sec = >300, SPA % = 0, MADR mg/mL = 0.6, VWF:Ag U/dL = 42.8, VWF:CB U/dL = 10.6, VWF:CB ratio = 0.25, VWF:RCo U/dL = 25.2, VWF:RCo ratio = 0.58, Platelet VWF U/dL = 132.7, FVIII U/dL = 47.1, BAT F/M = 10
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
heterozygous small deletion (p.Leu 757ValfsX22) together with a large deletion of exons 48–52
Case: IP-4
DiseaseAssertion: VWD3
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs:
CaseHPOFreeRext: VWF:Ag 3%
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Direct sequencing of exons 2–52 including exon/intron boundaries of the VWF gene
GenotypingMethod: multiple ligation‐dependent probe amplification (MLPA; using kit P011 and P012; MRC Holland, Amsterdam, the Netherlands) according to the manufacturer’s instructions. The PCR products were run on an ABI PRISM 3130XL sequencer with the GeneScan 500 LIZ size standard and analyzed using GeneMapper Software 5.0 (Applied Biosystems, Darmstadt, Germany). Dosage analysis based on a comparison between deleted and reference wild‐type DNA samples was performed using the Excel‐based software Coffalyser V9.4 (MRC Holland).
PreviouslyPublished: NA
Gene: VWF
Variant: p.Leu757ValfsX22
HGVS:
ClinVarID:
CAID:
gnomAD:
MultipleGeneVariants:
GeneName: VWF
Variant: deletion of exons 48-52
ClinVarID or CAID:
gnomAD:
homozygous large deletion of exon 6
Case: IP-1
DiseaseAssertion: VWD3
FamilyInfo: 6 additional family members, 5 heterozygous and 1 homozygous. All meet criteria of mild VWD1.
ParentalGenotype(s): NA
CasePresentingHPOs:
CaseHPOFreeRext: VWF antigen (VWF:Ag) of <1%, VWF ristocetin‐cofactor activity (VWF:RCo) of <6% and factor VIII activity (FVIII:C) of 5%
CaseNOTHPOs: NA
CaseNOTHPOFreeText: NA
CasePreviousTesting: Direct sequencing of exons 2–52 including exon/intron boundaries of the VWF gene
GenotypingMethod: multiple ligation‐dependent probe amplification (MLPA; using kit P011 and P012; MRC Holland, Amsterdam, the Netherlands) according to the manufacturer’s instructions. The PCR products were run on an ABI PRISM 3130XL sequencer with the GeneScan 500 LIZ size standard and analyzed using GeneMapper Software 5.0 (Applied Biosystems, Darmstadt, Germany). Dosage analysis based on a comparison between deleted and reference wild‐type DNA samples was performed using the Excel‐based software Coffalyser V9.4 (MRC Holland).
PreviouslyPublished: NA
Gene: VWF
Variant: deletion of exon 6
HGVS:
ClinVarID:
CAID:
gnomAD:
large deletion of exons 33–34
Case: IP-6
DiseaseAssertion: VWD2
FamilyInfo: Mother is unaffected carrier of F8 Asn2129Ser. The VWF deletion of exons 33-34 segregates in 5 other affected male family members including the father and a full brother of IP-6. The patient’s father displayed a significant decrease in VWF:Ag and VWF:RCo, 13% and 7%, respectively, FVIII: C of 18.5% and the VWF:RCo/VWF:Ag ratio of 0.5 pointing out to type 2 VWD.
ParentalGenotype(s): Mother is heterozygous for F8FAsn2129Ser. Father is heterozygous for VWF deletion of exons 33-34.
CasePresentingHPOs:
CaseHPOFreeRext: VWF:Ag (17%), VWF:RCo (9%) and FVIII:C (1,9%). Bleedings in the oral cavity, ankle joint and hematomas.
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Direct sequencing of exons 2–52 including exon/intron boundaries of the VWF gene
GenotypingMethod: multiple ligation‐dependent probe amplification (MLPA; using kit P011 and P012; MRC Holland, Amsterdam, the Netherlands) according to the manufacturer’s instructions. The PCR products were run on an ABI PRISM 3130XL sequencer with the GeneScan 500 LIZ size standard and analyzed using GeneMapper Software 5.0 (Applied Biosystems, Darmstadt, Germany). Dosage analysis based on a comparison between deleted and reference wild‐type DNA samples was performed using the Excel‐based software Coffalyser V9.4 (MRC Holland).
PreviouslyPublished: NA
Gene:VWF
Variant: deletion of exons 33-34
HGVS:
ClinVarID:
CAID:
gnomAD:
MultipleGeneVariants:
GeneName: F8
Variant: Asn2129Ser
ClinVarID or CAID:
gnomAD:
Case#: 27018, Age 31, Male, Blood Type O+ (Table S3)
Disease Assertion: VWD 1
FamilyInfo: The patient is one out of two members of Family#2709. Both patients variants were not determined.
Parental Genotype: Not listed
CasePresentingHPOs: N/A
CaseHPOFreeText: VWF:Ag:27, VWF:RCo:28.5, FVIII:C:59, VWF:CB:25
CaseNotHPOs: N/A
CaseNotHPOFreeText: Bleeding Score 2
Protein Expression: N/A
CasePreviousTesting: 48,48 Access-Array amplification. NGS Molecular analysis was performed. Sanger sequencing was used to validate selected mutations.
Gene: VWF
Variant: Not determined
ClinVar: N/A
CAID: N/A
gnomAD: N/A
Case: P78, Chinese, female, 23yo
DiseaseAssertion: VWD3
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type O blood, bleeding score = 13; VWF:Ag (%) = <0.3, VWF:RCo (%) = <0.5, FVIII:C (%) = 4.3, VWF:CB (%) = <0.5, VWFpp (%) = <0.5, VWF:RCo/VWF:Ag = NA, VWF:CB/VWF:Ag = NA, VWFpp/VWF:Ag = NA, FVIII:C/VWF:Ag = NA
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.5183_5186del - unregistered variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Case: P30, Chinese, female, 16yo
DiseaseAssertion: VWD3
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type O blood, bleeding score = 21; VWF:Ag (%) = 0.5, VWF:RCo (%) = <0.5, FVIII:C (%) = 2.0, VWF:CB (%) = 0.6, VWFpp (%) = <0.5`, VWF:RCo/VWF:Ag = NA, VWF:CB/VWF:Ag = 1.2, VWFpp/VWF:Ag = NA, FVIII:C/VWF:Ag = 4.0
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: Exons 6–16 del - unregistered variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Case: P89, Chinese, female, 51yo
DiseaseAssertion: VWD2N
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type O blood, bleeding score = 7; VWF:Ag (%) = 125.8, VWF:RCo (%) = 119.6, FVIII:C (%) = 9.8, VWF:CB (%) = 127.8, VWFpp (%) = 109.8, VWF:RCo/VWF:Ag = 1.0, VWF:CB/VWF:Ag = 1.0, VWFpp/VWF:Ag = 0.9, FVIII:C/VWF:Ag = 0.1, VWF: FVIIIB (%) = 0.1
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.2446C>T (p.Arg816Trp)
HGVS: NM_000552.4(VWF):c.2446C>T (p.Arg816Trp)
ClinVarID: 295; https://www.ncbi.nlm.nih.gov/clinvar/variation/295/
CAID: NA
gnomAD: MAF = 0.0002541 (9/35418 alleles) in the Latino/Admixed American population; https://gnomad.broadinstitute.org/variant/12-6145654-G-A?dataset=gnomad_r2_1
Case: P28, Chinese, male, 15yo
DiseaseAssertion: VWD2B
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type A blood, bleeding score = 4; VWF:Ag (%) = 17.7, VWF:RCo (%) = 4.9, FVIII:C (%) = 25.5, VWF:CB (%) = 5.1, VWFpp (%) = 45.3, VWF:RCo/VWF:Ag = 0.3, VWF:CB/VWF:Ag = 0.3, VWFpp/VWF:Ag = 2.6, FVIII:C/VWF:Ag = 1.4, RIPA (0.5 mg/ml, %) = 20.5, PLT(×109/l) = 112
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
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
Case: P81, Chinese, female, 30yo
DiseaseAssertion: VWD1
FamilyInfo: NA
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0012147
(Reduced quantity of VWF)
CaseHPOFreeText: type A blood, bleeding score = 7; VWF:Ag (%) = 5.0, VWF:RCo (%) = 5.3, FVIII:C (%) = 6.1, VWF:CB (%) = 6.8, VWFpp (%) = 46.0, VWF:RCo/VWF:Ag = 1.1, VWF:CB/VWF:Ag = 1.4, VWFpp/VWF:Ag = 9.2, FVIII:C/VWF:Ag = 1.2, RIPA (1.2 mg/ml, %) = 85.4
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NGS
PreviouslyPublished: NA
Gene: VWF
Variant: c.3614G>A (p.Arg1205His)
HGVS: NM_000552.4(VWF):c.3614G>A (p.Arg1205His)
ClinVarID: 308; https://www.ncbi.nlm.nih.gov/clinvar/variation/308/
CAID: NA
gnomAD: absent
An infant with presumed maternal immune thrombocytopenic purpura had persistent thrombocytopenia with platelet clumping. The patient had no significant bleeding symptoms in the first year of life and von Willebrand antigen and ristocetin cofactor activity were normal. Absent high molecular weight multimers ultimately led to a genetically proven diagnosis of type 2B von Willebrand disease (3964G>A VWF exon 28), highlighting the challenges of establishing this diagnosis in infants.
Case: Rotz Proband, female, reported at birth
DiseaseAssertion: VWD2b
FamilyInfo: Mother was 30yo reported with new onset thrombocytopenia during labor, diagnosed with maternal ITP; mother also had history of menorrhagia and excessive bleeding with minor trauma; VWF profile revealed a Factor VIII activity=49 IU/dL, VWF antigen=32 IU/dL, and undetectable RCo
ParentalGenotype(s): mother also carried c.3964G>A unregistered variant
CasePresentingHPOs: HP:0001873, HP:0030132, HP:0000967, HP:0000421, HP:0001892, HP:0001903, HP:0001981
(thrombocytopenia, Absence of large von Willebrand factor multimers, Petechiae, epistaxis, abnormal bleeding, anemia, schistocyte)
CaseHPOFreeText: small hematoma at IV puncture site, platelet count was 9×109/L, ultrasound showed no hemorrhage, hemoglobin=7.6 g/dL
CaseNOTHPOs: HP:0012147, HP:0030129
(Reduced quantity of VWF, impaired ristocetin cofactor assay activity)
CaseNOTHPOFreeText: no unusual findings on physical exam
CasePreviousTesting: NA
GenotypingMethod: Sequencing of VWF exon 28
PreviouslyPublished: NA
Gene: VWF
Variant: c.3964G>A unregistered variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
0.39
Case: 2A-4
DiseaseAssertion: VWD2A
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs: AcuStar RCo/Ag = 0.39; AcuStar CB/Ag = 0.17; ELISA CB/Ag = 0.20
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
Women with postpartum hemorrhage during follow‐up
Case:
DiseaseAssertion:
FamilyInfo:
ParentalGenotypes(s):
CasePresentingHPOs:
CaseHPOFreeText: bleeding score= 3, Prior PPH Yes,Prior HMB no
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
Gene: VWF
Variant:
HGVS:
ClinVar:
CAID:
gnomAD:
We were able to further investigate platelets and/or BOECs in one family with the Pro2808Leufs*24 variant. The pedigree and laboratory data is shown in Fig. 1. The IC, T105, is homozygous for Pro2808Leufs*24. One of her siblings heterozygous for the variant was also enrolled (T107).
Case: IC-T105, Canadian, female
DiseaseAssertion: VWD3
FamilyInfo: Pedigree in Fig 1A, 4 homozygotes, 3 heterozygotes
ParentalGenotype(s): not reported
CasePresentingHPOs:
CaseHPOFreeText: VWF:Ag = 0.02 IU/mL, VWF:RCo = 0.00 IU/mL, FVIII:C = 0.03, bleeding score = 18
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: sequencing of VWF gene
PreviouslyPublished: PMID:23311757
Gene: VWF
Variant: c.8419_8422dup (p.Pro2808Lysfs*24) - Unregistered Variant
HGVS: NA
ClinVarID: NA
CAID: NA
gnomAD: NA
Case: Case Report, female, 63yo
DiseaseAssertion: VWD2B
FamilyInfo: sister exhibited thrombocytopenia and mother had suffered from acute subdural hematoma in the context of chronic thrombocytopenia
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0002138, HP:0011854, HP:0001873, HP:0032044, HP:0030132
(Subarachnoid hemorrhage, Hemoperitoneum, thrombocytopenia, Decreased vigilance, Absence of large von Willebrand factor multimers)
CaseHPOFreeText: thrombocytopenia with pregnancy, platelet count fluctuated between 3 and 200 G/l, subarachnoid hemorrhage associated with a subdural hematoma after falling, hemostasis results were normal, meningeal hemorrhage, cephalalgia; FVIII:C: 1.63 IU/ml; VWF:RCo: 0.7 IU/ml; VWF:Ag: 1.8 IU/ml, ratio VWF:Rco/VWF/Ag: 0.39; Ristocetin-induced platelet agglutination could not be performed due to the severe thrombocytopenia
CaseNOTHPOs: NA
CaseNOTHPOFreeText: NA
CasePreviousTesting: tests for autoimmune disease negative
GenotypingMethod: NGS of exon 28 of VWF gene; variant confirmed via Sanger sequencing
PreviouslyPublished: NA
Gene: VWF
Variant: c.3946G>A (p.Val1316Met)
HGVS: NM_000552.4(VWF):c.3946G>A (p.Val1316Met)
ClinVarID: 290; https://www.ncbi.nlm.nih.gov/clinvar/variation/290/
CAID:
gnomAD: absent
T3-4
Case: T3-4, male, 16yo
DiseaseAssertion: VWD3
FamilyInfo:
ParentalGenotype(s):
CasePresentingHPOs:
CaseHPOFreeText: Blood type: A+, bleeding score = 24, VWF:Ag (IU/mL) = 0.01; VWF:RCo (IU/mL) = 0.03; FVIII:C (IU/mL) = 0.01
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting:
GenotypingMethod: qRT-PCR
PreviouslyPublished:
Gene: VWF
Variant 1: c.1657dupT (p.Trp553Leufs*97)
HGVS: n/a
ClinVarID: n/a
CAID: n/a
gnomAD: n/a
Variant 2: c.8419_8422dupTCCC (p.Pro2808Leufs*24)
HGVS: n/a
ClinVarID: n/a
CAID: n/a
gnomAD: n/a
7
Case#: Subject number 7, male, 62 years (diagnosis), 66 years (baseline visit), 67 years (ERT), 67 years (ventilation)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)
CaseHPOFreeText: mechanical ventilation at last visit
CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)
CaseNotHPOFreeText: no mechanical ventilation at Baseline 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
2
Case#: Subject number 2, female, 20 years (diagnosis), 48 years (baseline visit), 39 years (ERT), 34 years (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
30
Case#: Subject number 30, male, 12 years (baseline visit)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)
CaseHPOFreeText:
CaseNotHPOs: HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress), HP:0001324 (Muscle Weakness)
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
5
Case#: Subject number 5, female, 20 years (diagnosis), 45 years (baseline visit), 42 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
4
Case#: Subject number 4, female, 56 years (diagnosis), 63 years (baseline visit), 59 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
25
Case#: Subject number 25, male, 41 years (diagnosis), 46 years (baseline visit), 43 years (ERT), 43 (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
36
Case#: Subject number 36, male, 44 years (diagnosis), 49 years (baseline visit)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)
CaseHPOFreeText:
CaseNotHPOs: HP:0002098 (respiratory distress), HP:0002870 (obstructive sleep apnea), HP:0001324 (Muscle Weakness)
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
3
Case#: Subject number 3, female, 26 years (baseline visit)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)
CaseHPOFreeText:
CaseNotHPOs: HP:0002870 (obstructive sleep apnea), HP:0001324 (Muscle Weakness), 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
P4
Case#: Subject number 4, male, 5 months (onset), 34 months (first admission)
DiseaseAssertion: Pompe disease
FamilyInfo: "no family history of neuromuscular disorders"
CasePresentingHPOs: HP:0001712 (left ventricular hypertrophy), HP:0002194 (delayed gross motor development), HP:0004887 (respiratory failure requiring assisted ventilation), HP:0002090 (pneumonia), HP:0002205 (recurrent respiratory infections), HP:0003819 (death in childhood)
CaseHPOFreeText: ambulatory (transport ventilator), infantile-onset
CaseNotHPOs:
CaseNotHPOFreeText: no tracheostomy, no dysphagia at baseline, not on BiPAP
CasePreviousTesting: “GAA activity in peripheral blood leukocytes lower than normal”; on enzyme replacement therapy
P5
Case#: Subject number 5, male, 1 month (onset), 3 months (first admission)
DiseaseAssertion: Pompe disease
FamilyInfo: "no family history of neuromuscular disorders"
CasePresentingHPOs: HP:0001714 (ventricular hypertrophy), HP:0002194 (delayed gross motor development), HP:0004887 (respiratory failure requiring assisted ventilation), HP:0002205 (recurrent respiratory infections), HP:0002090 (pneumonia)
CaseHPOFreeText: infantile-onset, dysphagia at baseline, on BiPAP
CaseNotHPOs:
CaseNotHPOFreeText: no tracheostomy
CasePreviousTesting: “GAA activity in peripheral blood leukocytes lower than normal”; on enzyme replacement therapy
Pompe disease is an autosomal recessive inborn error of metabolism caused by mutations in the glucosidase alpha acid (GAA) gene located on the long arm of chromosome 17q25.2-q25.3.
PMID: 33202836
Gene: GAA
Disease: Pompe disease
Inheritance: Autosomal recessive
SK
PreviouslyPublished: PMID: 1317725
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: https://glanzmann.mcw.edu/
Patient P
Case40: Patient P
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: 44% GPIIIa and GPIIb surface expression
PlateletAggregation: N/A
CasePreviousTesting: N/A
Gene: ITGB3
Variant: NC_000017.11:g.47310169T>C
LegacyVariant: N/A
ClinVar: 13556
CAiD: CA123230
gnomAD: N/A
PreviouslyPublished: References 63-65
F10.II.3
Case#: Male 74 (age when studied)
Disease: Glazmann's Thrombasthenia Like Syndrome
CasePresentingHPOs: HP:0001873, HP:0005110, HP:0001638, HP:0000225, HP:0000978
Thrombocytopenia, Atrial fibrillation, cardiomyopathy, gingival bleeding, easy bruising
CaseNotHPOs: NA
FamilyInfo: Pedigree figure 1. Several affected family members, history of thrombocytopenia.
PlateletAgreggation:Daughter studied: Normal aggregation to epi and ADP, ristocetin not tested.
GenotypingMethod: Genetic analysis of ITGA2B and ITGB3 genes was performed by next-generation sequencing (NGS). Sanger sequencing used to confirm variants.
ClinVar: 50227
CAID: CA143709
Variant: NM_000212.3:c.2245G>C (ITGB3)
GnomAD: Not found
ExpressionEvidence: Level of expression on PLT surface determined by FCM: CD41a (GPIIb/IIIa) 66%, CD61 (GPIIIa) 65.5%, and CD42b (GPIb) 113%. Healthy control value range: CD41a (GPIIb/IIIa) (85-115%); CD61 (GPIIIa) (80-120%); CD42b (GPIb) (70-130%).
F7.II.2
Case#: Female, 45 (age of diagnosis)
Disease: Glazmann's Thrombasthenia Like Syndrome
CasePresentingHPOs: HP:0001873, HP:0100646
Thrombocytopenia, Thyroiditis
CaseNotHPOs: NA
FamilyInfo: Pedigree figure 1. Affected sister, family history of thrombocytopenia
PlateletAgreggation: 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: CA400034288
Variant: NM_000212.3:c.2243A>C (ITGB3)
GnomAD: Not Found
ExpressionEvidence: Level of expression on PLT surface determined by FCM: CD41a (GPIIb/IIIa) 65%, CD61 (GPIIIa) 58%, and CD42b (GPIb) 116%. Healthy control value range: CD41a (GPIIb/IIIa) (85-115%); CD61 (GPIIIa) (80-120%); CD42b (GPIb) (70-130%).
The affected female child
Case1: Female, Indian, age not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: Parents are heterozygous for the mutation of interest
CasePresentingHPOs: HP:0000978 (Easy bruising)
CaseHPOFreeText: Subsequent episodes of excessive bruising
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: Absent platelet aggregation in response to ADP, epinephrine and collagen but a normal response to ristocetin
CasePreviousTesting: Haplotype analysis was performed using polymorphic markers on chromosome 17q12–21, which included dinucleotide repeat polymorphisms (CA)n in BRCA1 gene and locus D17S579 and (CT)n within GP IIIa intron6, and the known restriction fragment length polymorphism(RFLP) markers, Fok I (GP IIb exon 26), Taq I (GP IIIa exon 8) andSma I (GP IIIa exon 9)
Gene: ITGB3
Variant: IVS1-14C>A (Unregistered Variant)
LegacyVariant: N/A
ClinVar: N/A
CAiD: N/A
gnomAD: N/A
Twins With an Identical Novel Mutation in ITGB3: A Case Report of Glanzmann Thrombasthenia–like Syndrome
PMID: 38151855
Gene: ITGB3
GNC: 6156
4CabGT-4
Case4: (Proband CabGT-4), Female, age not specified, Caucasian
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
ProteinExpression: Flow cytometry showed surface expression as 53% GPIIb and 66% GPIIIa
Platelet Aggregation: N/A
CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
Gene: ITGA2B
Variant: c.1442-13_1442-1del (This variant does not show up in the CAR or ClinVar)
LegacyVariant: N/A
ClinVar: N/A
CAiD: N/A
gnomAD N/A
WV
Case11: Patient WV, gender, age and ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 6
PlateletAggregation: See Table 6
CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries
Gene: ITGA2B
Variant: c.2232Gins (Noting this as an Unknown Variant as this won't show up in CAR-- I am sure there is a way to retrieve the CAiD; however, will need to discuss with senior biorcurator)
LegacyVariant: ^
ClinVar: ^
CAiD: ^
gnomAD: ^
Glanzmann’s thrombasthenia with spontaneous upper gastrointestinal bleeding: a case report
PMID: 32212884
The propositus (L.C.; II.1) in family 2 is a 17-yearold Portuguese girl
Case2: Female, 17 years old, Portugese
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Also studied were the patient’s mother (I.2), her father (I.1), and her brother (II.2). See pedigree below in article
ParentalGenotype: Parents were heterozygous for mutation
CasePresentingHPOs: HP:0000967
(Petechia)
CaseHPOFreeText: Mucocutaneous bleeding
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
ProteinExpression: <5% surface expression of aIIbb3
PlateletAggregation: Platelet aggregation is absent with ADP, collagen, epinephrine and arachidonic acid among agonists tested but the response was normal with ristocetin
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: N/A
CAiD:
gnomAD: MAF in the Other population is 0.0001629 https://gnomad.broadinstitute.org/variant/17-45369648-A-AC
Novel gene mutation in von Hippel-Lindau disease - a report of two cases
PMID: 31823746
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Mosaicism in von Hippel–Lindau disease with severe renal manifestations
PMID: 23384228
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Calculating optimal surveillance for detection of von Hippel–Lindau-related manifestations
PMID: 24132471
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Exploring the hereditary background of renal cancer in Denmark
PMID: 31034483
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Hypogonadotrophic hypogonadism due to intrasellar hemangioblastoma in von Hippel–Lindau syndrome† James C. Barton, Corresponding Author ironmd@dnamail.com Department of Medicine, Brookwood Medical Center, Birmingham, Alabama Department of Medicine, University of Alabama at Birmingham, Birmingham, AlabamaG105, 2022 Brookwood Medical Center Drive, Birmingham, AL 35209.Search for more papers by this authorEdison Goncalves, Department of Medicine, Brookwood Medical Center, Birmingham, AlabamaSearch for more papers by this authorAvni Santani, Department of Pathology and Laboratory Medicine, Molecular Genetics Laboratory, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorBalasundaram Chandra-Sekar, Department of Radiology, Brookwood Medical Center, Birmingham, AlabamaSearch for more papers by this authorE. Carter Morris, Department of Surgery, Brookwood Medical Center, Birmingham, AlabamaSearch for more papers by this authorBritton B. Carter, Department of Surgery, Brookwood Medical Center, Birmingham, AlabamaSearch for more papers by this authorCatherine A. Stolle, Department of Pathology and Laboratory Medicine, Molecular Genetics Laboratory, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this author
PMID: 19215058
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Head and Neck Paragangliomas in Von Hippel-Lindau Disease and Multiple Endocrine Neoplasia Type 2
PMID: 19336503
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Endolymphatic sac tumor (aggressive papillary tumor of middle ear and temporal bone): Report of two cases with analysis of the VHL gene
PMID: 18423895
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Endocrine Pancreatic Tumors in von Hippel-Lindau Disease
PMID: 18580449
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours
PMID: 19208735
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Unilateral Papillary Cystadenoma ofthe Epididymis as a First Presentationof Von Hippel-Lindau Disease
PMID:29729363 Gene:VHL StandardizedReferenceSequence: NM_000551.3
Percutaneous ultrasound-guided radiofrequency ablation treatment and genetic testing for renal cell carcinoma with Von Hippel-Lindau disease
PMID: 22398592
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germline VHL Mutation Discovered in Association with EGFR-Positive Lung Cancer and Metachronous Hepatocellular Carcinoma: A Case Report
PMID: 34720947
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
Rationalization of genetic testing in patients with apparently sporadic pheochromocytoma/paraganglioma
PMID: 19343621
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Obstructive jaundice due to von Hippel-Lindau disease-associated pancreatic lesions: A case report
PMID: 24959293
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Exploring the role of defective fibronectin matrix assembly in the VHL-associated CNS hemangioblastoma
PMID: 29813026
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Signal Peptide Variants that Impair Secretion of Pancreatic Secretory Trypsin Inhibitor (SPINK1) Cause Autosomal Dominant Hereditary Pancreatitis
PMID: 17274009
Gene: F9
HGNC: 3551
Functionally Important Regions of the Facr IX Gene Have aLow Rate of Polymorphism and a High Rate of Mutation in theDinucleotide CpG
PMID: 2773937
Gene: F9
HGNC: 3551
Blood Clotting Factor IX Niigata: Substitution of Alanine-390 byValine in the Catalytic Domain1
PMID: 3243764
Gene: F9
HGNC: 3551
Defective propeptide processing and abnormal activation underlie the molecular pathology of factor IX Troed-y-Rhiw
PMID: 2788012
Gene: F9
HGNC: 3551
Germline mutations in Peruvian patients with hemophilia B: pattern of mutation in AmerIndians is similar to the putative endogenous germline pattern
PMID: 9600455
Gene: F9
HGNC: 3551
Genetic basis and carrier detection of hemophilia B of Chinese origin
PMID: 8470048
Gene: F9
HGNC: 3551
Incidental finding of unreported large duplication in F8 gene during prenatal analysis: Which management for genetic counselling?
PMID: 31445452
Gene: F8
Molecular epidemiology of factor IX germline mutations in Mexican Hispanics: pattern of mutation and potential founder effects
PMID: 8772212
Gene: F9
HGNC: 3551
Parental Origin of Factor IX Gene Mutations, and TheirDistribution in the Gene
PMID: 1346077
Gene: F9
HGNC: 3551
Theoretical investigation of the structure, detonation properties, and stability of bicyclo[3.2.1]octane derivatives
PMID: 31359151
Gene: F8
No Evidence: This article does not mention F8 or Hemophilia
Liver transplantation is a plausible, effective and safe procedure in patients with hemophilia. Clinical case
PMID: 31344177
Gene: F8
No Evidence: No variant evidence given in this article; however, patient with Hemophila A is described here.
In silico analysis of missense mutations in exons 1–5 of the F9 gene that cause hemophilia B
PMID: 31253089
Gene: F9
HGNC: 3551
Molecular defects in haemophilia B: detection by direct restriction enzyme analysis
PMID: 1680373
Gene: F9
HGNC: 3551
Compensated pathogenic variants in coagulation factors VIII and IX present complex mapping between molecular impact and hemophilia severity
PMID: 31267011
Gene: F9
HGNC: 3551
F9 missense mutations impairing factor IX activation areassociated with pleiotropic plasma phenotypes
PMID: 34626083
Gene: F9
HGNC: 3551
Regulation of a strong F9 cryptic 5′ss by intrinsic elements and by combination of tailored U1snRNAs with antisense oligonucleotides
PMID: 26063760
Gene: F9
HGNC: 3551
Molecular pathology of haemophilia B: identification of five novel mutations including a LINE 1 insertion in Indian patients
PMID: 15086324
Gene: F9
HGNC: 3551
Twenty-four novel hemophilia B mutations revealed by rapid scanning of the whole factor IX gene in a French population sample
PMID: 8055323
Gene: F9
HGNC: 3551
Therapeutic potential of spheroids of stem cells from human exfoliated deciduous teeth for chronic liver fibrosis and hemophilia A
PMID: 31552493
Gene: F8
No Evidence: No mention of variants or probands in this article.
High resolution melting for F9 gene mutation analysis in patients with haemophilia B
PMID: 29517974
Gene: F9
HGNC: 3551
Novel Mutations in Factor IX Gene From Western IndiaWith Reference to Their Phenotypic andHaplotypic Attributes
PMID: 19262239
Gene: F9
HGNC: 3551
PMID: 10094553
Gene: F9
HGNC: 3551
A short term anatomical and visual outcomes of large idiopathic macular holes surgery following inverted internal limiting membrane fl ap technique
PMID: 31523064
Gene: F8
NoEvidence: This article does not mention Hemophilia A, or F8. No mention of blood disorders in general.
Molecular pathology of haemophilia B
PMID: 2743975
Gene: F9
HGNC: 3551
Whole-exome sequencing in 168 Korean patients with inherited retinal degeneration
PMID: 33691693
Gene: TOPORS
PMID: 19853238
Gene: BEST1
Autosomal dominant pericentral retinal dystrophy caused by a novel missense mutation in the TOPORS gene
PMID: 19183411
Gene: TOPORS
Molecular Epidemiology in 591 Italian Probands With Nonsyndromic Retinitis Pigmentosa and Usher Syndrome
PMID: 33576794
Gene: TOPORS
Mutations in TOPORS Cause Autosomal Dominant Retinitis Pigmentosa with Perivascular Retinal Pigment Epithelium Atrophy
PMID: 17924349
Gene: TOPORS
[Mutation analysis and prenatal diagnosis of 2 cases with mucopolysaccharidosis type I]
PMID: 21624210
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Patient of family D
Case#: Family D proband, female, 2 months and 5 days old (age of diagnosis), 14 months old (age of onset), 10 years old (age at report), Tunisia.
DiseaseAssertion: MPS1-H
FamilyInfo: No affected family members (See Fig. 1), parents were 1st degree relatives (first cousins) (See Table 1).
CasePresentingHPOs: HP:0002094, HP:0001605, HP:0001999, HP:0004322 (Dyspnea, laryngeal paralysis, abnormal facial shape, short stature)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: IDUA activity (0.1 nmol/h/mg) (usual values: 1-5).
CaseUrineGAGs: glycosaminoglycans (97 mg/g of creatinine) (usual values: 9-46), abnormal electrophoresis profile with dermatan sulfate and heparan sulfate.
CaseERT: N/A
CaseBMT: N/A
Variant1: c.1743C>G (p.Y581X)
Variant1ClinVarID: 550883
Variant1CAID: N/A
Variant2: c.1743C>G (p.Y581X)
Variant2ClinVarID: 550883
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Residual α-l-iduronidase activity in fibroblasts of mild to severe Mucopolysaccharidosis type I patients
PMID: 23786846
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
30.163 (2.3)4.3DS 128.41 homozygous pathogenic: c.208C>T; p.Q70*Severe MPS I
Case#:Patient Sample unique ID 3, 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:Severe MPS1, Hurler Syndrome
FamilyInfo:None
CasePresentingHPOs: HP:0007957 (mild corneal clouding), HP:0011729 (decreased joint range of motion), HP:0008454 (lumbar kyphosis)
CaseHPOFreeText: A history of multiple failed hearing tests, chronic serous otitis media, and pressure equalizer tube placement
CaseNotHPOs:None
CaseNotHPOFreeText: None
CaseEnzymeAssay: IDUA activity 0.163 (2.3) umol/L/h (%DMA) through dried blood spot during newborn screening and 4.3 pmol/punch/h Confirmatory IDUA enzyme
CaseUrineGAGs: DS 128.4 g/mol creatinine and HS 466.6 g/mol creatinine
CaseERT:No
CaseBMT: The patient received a cord blood transplantation at 7 months of age.
Variant1:1 homozygous pathogenic: c.208C>T; p.Q70* (∗ IDUA enzyme activity reference range is < 8.0 pmol/punch/hour.)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2:1 homozygous pathogenic: c.208C>T; p.Q70* (∗ IDUA enzyme activity reference range is < 8.0 pmol/punch/hour.)
Variant2ClinVarID: 11909
Variant2CAID: CA204563
AdditionalVariants:N/A
ParentalGenotype:N/A
PreviouslyPublished:N/A
Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up
PMID: 20026495
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Mucopolysaccharidosis type I: molecular characteristics of two novel alpha-L-iduronidase mutations in Tunisian patients
PMID: 21639919
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review
PMID: 37239976
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
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: X654C
Variant1ClinVarID: Not sure how to look up in CAR
Variant1CAID: Not sure how to look up in CAR
Variant2: N/A
Variant2ClinVarID: N/A
Variant2CAID: N/A
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished: N/A
3
Case#: Patient No. 3 (Table 1), White race, female, 1.95 years old (age at time of gene therapy), 75 IQ score, 2.13 years since gene therapy (2 years since latest visit).
DiseaseAssertion: MPS-IH
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: N/A
CaseUrineGAGs: N/A
CaseERT: N/A
CaseBMT: Yes
Variant1: c.208C>T (p.Q70X)
Variant1ClinVarID: 11909
Variant1CAID: CA204563
Variant2: c.208C>T (p.Q70X)
Variant2ClinVarID: 11909
Variant2CAID: CA204563
AdditionalVariants: N/A
ParentalGenotype: N/A
PreviouslyPublished N/A
Identification of an α-l-iduronidase (IDUA) M1T mutation in a Chinese family with autosomal recessive mucopolysaccharidosis I
PMID: 37347427
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
Identification of infants at risk for developing Fabry, Pompe or Mucopolysaccharidosis-I from newborn blood spots by tandem mass spectrometry
PMID:23465405
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
PMID: 8213840
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive