PMID: 27819553

Gene: GP1BA

HGNCID: 4439

Case: Case 2, male, hispanic, symptom onset at birth

DiseaseAssertion: Platelet-type VWD (PT-VWD)

FamilyInfo: Parents were tested for platelet antigen 5a (HPA5a): mother was negative and father was positive, parents had normal VWD panels including VWF multimer and RIPA test

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0004846, HP:0000978, HP:0001873, HP:0012541, HP:0030132

(Prolonged bleeding after surgery, easy bruising, thrombocytopenia, Cephalohematoma, Absence of large von Willebrand factor multimers)

CaseHPOFreeText: peripheral blood smear showed platelet clumping and large granular platelets, Platelet (×109/L) = 61, Factor VIII (IU/mL) = 0.94, VWF:Ag (IU/mL) = 0.88, VWF:RCo (IU/mL) = 0.34, VWF:CB (IU/mL) = ND, RCo/Ag ratio = 0.39, CB/Ag ratio = NA, VWF: HMW Multimers = absent

CaseNOTHPOs: NA

CaseNOTHPOFreeText: umbilical cord bleeding, bleeding after heel stick

CasePreviousTesting: no mutations in exon 28 of VWF gene

GenotypingMethod: NA

PreviouslyPublished: NA

Gene: GP1BA

Variant: c.763A>G (p.Met255Val)

HGVS: NM_000173.7(GP1BA):c.763A>G (p.Met255Val)

ClinVarID: 4155; https://www.ncbi.nlm.nih.gov/clinvar/variation/4155/

CAID:

gnomAD: absent

Case: Case 3, female

DiseaseAssertion: Platelet-type VWD (PT-VWD)

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0000132, HP:0004846, HP:0001873, HP:0030129, HP:0030132

(easy bruising, epistaxis, Menorrhagia, Prolonged bleeding after surgery, thrombocytopenia, Impaired ristocetin cofactor assay activity, Absence of large von Willebrand factor multimers)

CaseHPOFreeText: pregnancy complicated by progressive thrombocytopenia; Platelet (×109/L) = 135, Factor VIII (IU/mL) = 0.78, VWF:Ag (IU/mL) = 0.69, VWF:RCo (IU/mL) = 0.22, VWF:CB (IU/mL) = ND, RCo/Ag ratio = 0.32, CB/Ag ratio = ND, VWF: HMW Multimers = absent

CaseNOTHPOs: NA

CaseNOTHPOFreeText: NA

CasePreviousTesting: NA

GenotypingMethod: NA

PreviouslyPublished: NA

Gene: GP1BA

Variant: c.746G>T (p.Gly249Val)

HGVS: NM_000173.7(GP1BA):c.746G>T (p.Gly249Val)

ClinVarID: 4153; https://www.ncbi.nlm.nih.gov/clinvar/variation/4153/

CAID:

gnomAD: absent

Case: Case 1, male, 13yo at assessment, symptom onset at 45 days old

DiseaseAssertion: Platelet-type VWD (PT-VWD)

FamilyInfo: 1 symptomatic sister (menorrhagia, hemorrhagic follicular cyst); 1 asymptomatic sister; 3 brothers: twin died at 45days old due to leukemia, 1 symptomatic with daily epistaxis, 1 asymptomatic; father had bleeding symptoms; mom had severe bleeding with c-section requiring hysterectomy

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0001973, HP:0001892, HP:0000421, HP:0000979, HP:0001873, HP:0002090, HP:0000023, HP:0030132, HP:0011871

(Autoimmune thrombocytopenia, abnormal bleeding, epistaxis, purpura, thrombocytopenia, pneumonia, inguinal hernia, Absence of large von Willebrand factor multimers, impaired RIPA)

CaseHPOFreeText: bleeding treated with intravenous gamma-globulin (IVIg) and corticosteroids, laparoscopic splenectomy complicated by massive intraperitoneal bleeding, multiple bone marrow aspirations performed; born via c-section of twin pregnancy due to placenta previa; mepacrine uptake assay by flow cytometry was normal, Blood smear showed very large platelets with clear signs of activation and pseudopods; Platelet (×109/L) = 95, Factor VIII (IU/mL) = 1.00, VWF:Ag (IU/mL) = 1.29, VWF:RCo (IU/mL) = 0.28, VWF:CB (IU/mL) = 0.70, RCo/Ag ratio = 0.22, CB/Ag ratio = 0.54, VWF: HMW Multimers = partial loss

CaseNOTHPOs: NA

CaseNOTHPOFreeText: NA

CasePreviousTesting: NA

GenotypingMethod: NA

PreviouslyPublished: NA

Gene: GP1BA

Variant: c.763A>G (p.Met255Val)

HGVS: NM_000173.7(GP1BA):c.763A>G (p.Met255Val)

ClinVarID: 4155; https://www.ncbi.nlm.nih.gov/clinvar/variation/4155/

CAID:

gnomAD: absent

Case: Case 4, female, 5yo at onset, 20yo at report

DiseaseAssertion: Platelet-type VWD (PT-VWD)

FamilyInfo: Fhx of VWD; father diagnosed with type 2B VWD

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0000132, HP:0001873, HP:0004846

(easy bruising, epistaxis, menorrhagia, thrombocytopenia, Prolonged bleeding after surgery)

CaseHPOFreeText: pregnancy complicated by thrombocytopenia, Platelet aggregation studies were normal to ADP, epinephrine, collagen, and arachidonic; Platelet (×109/L) = 156, Factor VIII (IU/mL) = ND, VWF:Ag (IU/mL) = 0.57, VWF:RCo (IU/mL) = 0.86, VWF:CB (IU/mL) = ND, RCo/Ag ratio = 1.15, CB/Ag ratio = ND, VWF: HMW Multimers = normal

CaseNOTHPOs: NA

CaseNOTHPOFreeText: NA

CasePreviousTesting: no mutations in exon 28 of the VWF gene

GenotypingMethod: NA

PreviouslyPublished: NA

Gene: GP1BA

Variant: c.746G>T (p.Gly249Val)

HGVS: NM_000173.7(GP1BA):c.746G>T (p.Gly249Val)

ClinVarID: 4153; https://www.ncbi.nlm.nih.gov/clinvar/variation/4153/

CAID:

gnomAD: absent