Case1: Female, 6 months old, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo:

ParentalGenotype: Mother: Met124Val and Father: Asp119Tyr

CasePresentingHPOs: HP:0003010

(Prolonged bleeding time)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Diminished platelet content of αIIbβ3 in the proband (See Figure 1A)

PlateletAggregation: The platelets from the patient did not show aggregation upon stimulation with collagen, ADP, adrenaline, or arachidonic acid, but a response to ristocetin was observed

CasePreviousTesting: The entire coding sequences of ITGA2B and ITGB3 were determined by PCR amplification of overlapping fragments from total RNA

Gene: ITGB3

Variant: NM_000212.2:c.433G>T (p.Asp119Tyr) and NM_000212.2:c.448A>G (p.Met124Val)

LegacyVariant: N/A

ClinVar: 13554

CAiD: CA123226 and CA8622961

gnomAD: MAF in the South Asian population is 0.00003266 http://gnomad.broadinstitute.org/variant/17-45361895-A-G

Case1: GT-1, gender, age, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type II

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 revealed αIIbβ3 expression between 5% and 20%

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: ITGB3

Variant: NM_000212.2:c.448A>G (p.Met150Val) and NM_000212.2:c.774_775del (p.Cys258Ter)

LegacyVariant: (p.Met124Val)

ClinVar: N/A

CAiD: CA8622961 and CA915940285

gnomAD: MAF in South Asian population is 0.00003266 http://gnomad.broadinstitute.org/variant/17-45361895-A-G

PreviouslyPublished PMID: 15583747 (p.Met124Val)

Table 3 Molecular Diagnosis of Patients with Glanzmann Thrombasthenia:

Case1: GT-1, age, gender, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type II

FamilyInfo: Segregation analysis confirmed in presence of heterozygous mutations in this proband.

ParentalGenotype: Although segregation analysis confirmed, we do not know which variant in particular came from mom or dad.

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients presented with a variable bleeding diathesis; most patients had epistaxis (54%), cutaneous bleeding (58%), and menorrhagia (100% of women) while other common symptoms (oral cavity, GI, following dental extraction of mild injuries, postpartum, or hematomas) were in general milder. There is no specific phenotypes attached to probands in this paper.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed that αIIbβ3 expression was between 5% and 20%

PlateletAggregation: There was severely impaired aggregation in response to all physiological agonists, and ristocetin induced platelet agglutination was normal or reduced to some extent.

CasePreviousTesting: Total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Then, using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing. Every mutation found in cDNA was confirmed in DNA samples.

Gene: ITGB3

Variant: NM_000212.2:c.448A>G (p.Met124Val) and NM_000212.2:c.774_775del (p.Cys258Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622961 and CA915940285

gnomAD: MAF in South Asian population is 0.00003266 http://gnomad.broadinstitute.org/variant/17-45361895-A-G