Case9: No assertion made on age, gender or ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The identified variants were heterozygote in parents.

CasePresentingHPOs: HP:0005542

(Prolonged clotting time)

CaseHPOFreeText: Bleeding time greater than 20 minutes and hematocrit of 38.1%

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: Genetic study of patient was conducted using direct sequencing of entire coding and exon-intron boundaries of the ITGA2B and ITGB3 genes.

Gene: ITGA2B

Variant: NM_000419.3:c.1392A>G (p.Pro464Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA500273575

gnomAD: https://gnomad.broadinstitute.org/variant/17-42458248-T-C

Case1: Female, 35 years old, Italian

DiseaseAssertion: Macrothromocytopenia

FamilyInfo: See Supp. Fig S1 for pedigree

ParentalGenotype: See Supp. Fig S1 for pedigree

CasePresentingHPOs: N/A

CaseHPOFreeText: Life-long moderate to severe bleeding, mainly mucocutaneous

CaseNotHPOs: N/A

CaseNotHPOsFreeText: No abnormalities in blood clotting

ProteinExpression: Flow cytometry showed mild reduction of surface αIb β3

PlateletAggregation: Impaired platelet aggregation to physiological agonists but not to ristocetin,

CasePreviousTesting: ITGA2B and ITGB3 were amplified and sequenced

Gene: ITBG3

Variant: NM_000212.2:c.2134+1G>C

LegacyVariant: N/A

ClinVar: 50228

CAiD: CA143711

gnomAD: N/A

Case4: Patient M4, Male, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree It shows this patient is unaffected

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case8: Patient M8, Male, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case3: Patient M3, Male, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree It shows this patient is unaffected

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case2: Patient M2, Female, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case9: Patient M9, Male, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case5: Patient M5, Female, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case10: Patient M10, Male, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case1: Patient M1, Female, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case2: Patient 2, Male, 4 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother is Patient 1

ParentalGenotype: Mother and father revealed heterozygosity for c.1878G>C mutation. (Parents are consanguineous)

CasePresentingHPOs: HP:0000967 (Petechiae)

CaseHPOFreeText: Hematomas, prolonged in vitro bleeding time

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis revealed that there was 109 of GPIIb/IIIa expression for Patient 2

PlateletAggregation: All patients' platelets showed severely reduced platelet aggregation after stimulation with collagen and ADP in contrast to the normal range (See Table 1). Stimulation with epinephrine and arachidonic acid also demonstrated decreased platelet aggregation. In contrast, ristocetin-induced platelet aggregation was borderline for Patient 2

CasePreviousTesting: Sequenced ITGA2B and ITGB3 genes from one patient of each family (Patient 2 and 3) and Patient 1 and 4 were screened for the identified mutation in the corresponding family.

Gene: ITGA2B

Variant: NM_000419.3:c.1878G>C (p.Gln626His)

LegacyVariant: N/A

ClinVar: 2903

CAiD: CA115852

gnomAD: N/A

Case1: Patient 1, Male, 6 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother is Patient 2

ParentalGenotype: Mother and father revealed heterozygosity for c.1878G>C mutation. (Parents are consanguineous)

CasePresentingHPOs: HP:0000967, HP:0000421, HP:0000225

(Petechiae, epistaxis, gingival bleeding)

CaseHPOFreeText: Hematomas,

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis showed that there was no surface expression of GPIIb/IIIa detectable on patient 1's platelets, indicating a lack of platelet GPIIb/IIIa expression

PlateletAggregation: All patients' platelets showed severely reduced platelet aggregation after stimulation with collagen and ADP in contrast to the normal range (See Table 1). Stimulation with epinephrine and arachidonic acid also demonstrated decreased platelet aggregation. In contrast, ristocetin-induced platelet aggregation was within normal range for patient 1

CasePreviousTesting: Sequenced ITGA2B and ITGB3 genes from one patient of each family (Patient 2 and 3) and Patient 1 and 4 were screened for the identified mutation in the corresponding family.

Gene: ITGA2B

Variant: NM_000419.3:c.1878G>C (p.Gln626His)

LegacyVariant: N/A

ClinVar: 2903

CAiD: CA115852

gnomAD: N/A

Case1: (GT1), Gender, age and ethnicity not reported

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: 1 brother and 1 sister that are both heterozygous for g.951G>A and p.Leu343Pro

ParentalGenotype: Father: heterozygous for g.951G>A and p.Leu343Pro and Mother: heterozygous for both just like dad

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: ITGA2B

Variant: NC_000017.11:g.44393555C>T (g.951G>A promoter variant) and NM_000419.3:c.1028T>C (p.Leu343Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913189168 (promoter variant) and CA399804619 (p.Leu343Pro)

gnomAD N/A

Case3: (GT54), Gender, age and ethnicity not reported

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: 1 sister that are heterozygous for g.951G>A and p.Leu343Pro

ParentalGenotype: Father: heterozygous for g.951G>A and p.Leu343Pro and Mother: heterozygous for both just like dad

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: ITGA2B

Variant: NC_000017.11:g.44393555C>T (g.951G>A promoter variant) and NM_000419.3:c.1028T>C (p.Leu343Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913189168 (promoter variant) and CA399804619 (p.Leu343Pro)

gnomAD N/A

Case34: (GT15) Gender, age and ethnicity have not been specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother and father are heterozygous for this 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: ITGA2B

Variant: NM_000419.3:c.1753-1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802017

gnomAD N/A

Case16: (GT28) Gender, age and ethnicity is not reported

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Sister is heterozygous for the mutation

ParentalGenotype: Mother and father are both heterozygous for the mutation

CasePresentingHPOs:

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.1031A>G (p.Tyr344Cys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025816

gnomAD N/A

Case19: (GT53) Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Has a sister who does not have either of the 2 mutations (normal)

ParentalGenotype: Father: Does not have the Asp139His mutation but is heterozygous for the Tyr141Cys mutation. Mother: Heterozygous for the Asp139His mutation and is normal or does not harbor the Tyr141Cys 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: NG_008332.2:g.35655G>C (p.Asp139His) and NM_000212.2:c.422A>G (p.Tyr141Cys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400021843 and CA40002188, respectively as shown above

gnomAD N/A

Case36: (GT19) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: One brother is homozygous for the mutation and the other brother is heterozygous for the mutation

ParentalGenotype: Mother and father are 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: ITGA2B

Variant: There seems to be a typo in this variant, asked Shruthi NM_000419.3:c.937G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290954329

gnomAD MAF in the European (non-Finnish) population is 0.000008888 https://gnomad.broadinstitute.org/variant/17-42461461-C-T

Case32: (GT59) Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Has one normal borther and one brother who is heterozygous for the mutation

ParentalGenotype: Both parents are heterozygous for this mutation that the proband harbors

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.155_156delinsTT

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940691

gnomAD N/A

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

Case14: (GT2), Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: His sister is heterozygous for this mutation

ParentalGenotype: Father and mother are both heterozygous for this 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.725G>A (p.Arg242Gln) There is a typo in the paper-- it says that the c. is c.752G>A however it is 725

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224896

gnomAD N/A

Case33: (GT23) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Both brothers are heterozygous for this mutation and sister is normal

ParentalGenotype: Father is heterozygous for the NM_000419.3:c.800-2A>T mutation and mother does not harbor this mutation. Mother is heterozygous for the NM_000419.3:c.1210+4A>G mutation and father does not have this mutation.

CasePresentingHPOs:

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: ITGA2B

Variant: NM_000419.3:c.800-2A>T and NM_000419.3:c.1210+4A>G

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805150 and CA915940692

gnomAD N/A

Case2: GT18, Gender, age, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: 1 brother is heterozygous for the g.951G>A promoter variant and does not have the other Leu343Pro mutation and one brother is normal and does not have the NM_000419.3:c.2915dup mutation

ParentalGenotype: Father: homozygous for the g.951G>A promoter variant and the Leu343Pro Mother: is heterozyous for both those mutations and mother does not have NM_000419.3:c.2915dup while the father is heterozygous for NM_000419.3:c.2915dup

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: ITGA2B

Variant: NC_000017.11:g.44393555C>T (g.951G>A promoter variant) and NM_000419.3:c.1028T>C (p.Leu343Pro) and NM_000419.3:c.2915dup

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913189168 (promoter variant) and CA399804619 (p.Leu343Pro) and CA8602531

gnomAD MAF in the East Asian population is 0.0001088 https://gnomad.broadinstitute.org/variant/17-42452054-C-CG for the NM_000419.3:c.2915dup variant

Case28: (GT30) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother and father are 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.674del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940689

gnomAD N/A

Case26: (GT20) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Brother is homozygous for the mutation and the second brother is heterozygous

ParentalGenotype: Mother and father are 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: ITGA2B

Variant: NM_000419.3:c.1424_1427dup

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8603099

gnomAD MAF in the South Asian population is 0.0001960 https://gnomad.broadinstitute.org/variant/17-42457979-C-CACCT

Case2: Female, Israeli-Arab, (age is either 3 or 8)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 1C for pedigree

ParentalGenotype: See Fig 1C for pedigree

CasePresentingHPOs: HP:0000421, HP:0031364, HP:0000967, HP:0002239

(Severe epistaxis, ecchymosis, petechiae, GI bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: No surface expression of αIIbβ3 was found in patients’ platelets (See Fig 3)

PlateletAggregation: N/A

CasePreviousTesting: DNA fragments containing exons and flanking intronic regions of the aIIb and B3 genes were amplified by PCR using primers

Gene: ITGA2B

Variant: NM_000419.3:c.97A>G (p.Asn2Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399806951

gnomAD: N/A

Case1: Male, Israeli-Arab, (age is either 10 or 14)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 1C for pedigree

ParentalGenotype: See Fig 1C for pedigree

CasePresentingHPOs: HP:0000421, HP:0031364, HP:0000967

(Severe epistaxis, ecchymosis, petechiae)

CaseHPOFreeText: Decline of hemoglobin levels to 5 g dl each time epistaxis occurred

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: No surface expression of αIIbβ3 was found in patients’ platelets (See Fig 3)

PlateletAggregation: N/A

CasePreviousTesting: DNA fragments containing exons and flanking intronic regions of the aIIb and B3 genes were amplified by PCR using primers

Gene: ITGA2B

Variant: NM_000419.3:c.97A>G (p.Asn2Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399806951

gnomAD: N/A

Case3: Male, Israeli-Arab, (age is either 10 or 14)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 1C for pedigree

ParentalGenotype: See Fig 1C for pedigree

CasePresentingHPOs: HP:0000421, HP:0031364, HP:0000967

(Severe epistaxis, ecchymosis, petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: No surface expression of αIIbβ3 was found in patients’ platelets (See Fig 3)

PlateletAggregation: Absent platelet aggregation in response to ADP, epinephrine, collagen and normal ristocetin-induced platelet agglutination

CasePreviousTesting: DNA fragments containing exons and flanking intronic regions of the aIIb and B3 genes were amplified by PCR using primers

Gene: ITGA2B

Variant: NM_000419.3:c.97A>G (p.Asn2Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399806951

gnomAD: N/A

Case3: Male, 10 years old, Korean

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Figure 1 shows haplotype analysis

CasePresentingHPOs: HP:0001342

(Cerebral hemorrhage)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analyses revealed decreased expression at 7.2%/5.0% of the normal amount of CD41/CD61

PlateletAggregation: Platelet aggregation tests were performed to evaluate responses to ADP, collagen, epinephrine, and ristocetin agonists

CasePreviousTesting: Polymerase chain reaction for all exons ofITGA2Band/orITGB3were performed using primers. Sequence analysis was performed with reference to M_000419.3 andNP_000410.2 forITGA2Band NM_000212.2 and NP_000203.2 for ITGB3.

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) and NM_000419.3:c.975del

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544 and CA915940385

gnomAD: MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-42453691-T-G

Case4: Male, 4 years old, Korean

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Figure 1 shows haplotype analysis

CasePresentingHPOs: HP:0000978, HP:0000967

(Easy bruising, petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analyses revealed decreased expression at a level of 7.5%(type II GT)

PlateletAggregation: Platelet aggregation tests were performed to evaluate responses to ADP, collagen, epinephrine, and ristocetin agonists

CasePreviousTesting: Polymerase chain reaction for all exons of ITGA2Band/orITGB3were performed using primers. Sequence analysis was performed with reference to M_000419.3 andNP_000410.2 for ITGA2B and NM_000212.2 and NP_000203.2 for ITGB3.

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) and NM_000419.3:c.1750C>T (p.Arg584Ter)

LegacyVariant: N/A

ClinVar: 225393 and 2892

CAiD: CA290947544 and CA115834

gnomAD: MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-42453691-T-G and MAF in the East Asian population is 0.0002176 http://gnomad.broadinstitute.org/variant/17-42457372-G-A

Case1: Male, 2 years old, Korean

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Figure 1 shows haplotype analysis

CasePresentingHPOs: HP:0000978, HP:0000967

(Easy bruising, petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analyses revealed markedly decreasedCD41/CD61 expression (<1%) in Patient 1 (type I GT).

PlateletAggregation: Platelet aggregation tests were performed to evaluate responses to ADP, collagen, epinephrine, and ristocetin agonists

CasePreviousTesting: Polymerase chain reaction for all exons ofITGA2Band/orITGB3were performed using primers. Sequence analysis was performed with reference to M_000419.3 andNP_000410.2 forITGA2Band NM_000212.2 and NP_000203.2 for ITGB3.

Gene: ITGB3

Variant: NM_000212.2:c.1913+5G>T

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623377

gnomAD: MAF in the East Asian population is 0.0001633 http://gnomad.broadinstitute.org/variant/17-45376901-G-T

Case2: Male, 38 years old, Korean

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Figure 1 shows haplotype analysis

CasePresentingHPOs: HP:0004406, HP:0000225

(Recurrent epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analyses revealed markedly decreasedCD41/CD61 expression (<1%) in Patient 2 (type I GT).

PlateletAggregation: Platelet aggregation tests were performed to evaluate responses to ADP, collagen, epinephrine, and ristocetin agonists

CasePreviousTesting: Polymerase chain reaction for all exons ofITGA2Band/orITGB3were performed using primers. Sequence analysis was performed with reference to M_000419.3 andNP_000410.2 forITGA2Band NM_000212.2 and NP_000203.2 for ITGB3.

Gene: ITGB3

Variant: NM_000212.2:c.1913+5G>T

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623377

gnomAD: MAF in the East Asian population is 0.0001633 http://gnomad.broadinstitute.org/variant/17-45376901-G-T

Case15: GT-15, German, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.1594T>C heterozygous and Father: n/a

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGB3

Variant: NM_000212.2:c.1594T>C and NM_000212.2:c.2014+1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400029953 and CA400033055

gnomAD: N/A

Case10: GT-10, Caucasian, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: 3091delC heterozygous and Father: c.1210_105A>G heterozygous

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGA2B

Variant: NM_000419.3:c.1210+105A>G and NM_000419.3:c.3091del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290953790 and CA915940322

gnomAD: N/A

Case2: GT-2, German, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.31T>C heterozygous and Father: c.1458T>C heterozygous

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGB3

Variant: NM_000212.2:c.31T>C and for the second variant c.1458T>C -this does not show up in ensembl it says that the actual alleles are C>T

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291240306

gnomAD: N/A

Case9: GT-9, Caucasian, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.1186G>A heterozygous and Father: c.3060_2T>C heterozygous

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGA2B

Variant: NM_000419.3:c.1186G>A and NM_000419.3:c.3060+2T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399804315 and CA290944108

gnomAD: MAF in the South Asian population is 0.00006622 http://gnomad.broadinstitute.org/variant/17-42460885-C-T and MAF in the European non-Finnish population is 0.00003876 http://gnomad.broadinstitute.org/variant/17-42451720-A-G

Case11: GT-11, Arab, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.3092delT heterozygous and Father: deceased

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGA2B

Variant: NM_000419.3:c.641T>C and NM_000419.3:c.3092delT

LegacyVariant: N/A

ClinVar: 2901

CAiD: CA115848 and CA915940323

gnomAD: N/A

Case7: GT-7, German and Jugoslav, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.1126-72C>T heterozygous and Father: c.1126-72C>T heterozygous

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGB3

Variant: NM_000212.2:c.1030dup and an Unregistered Variant (c.1126_72C>T) (Does not show up in CAR)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA658820875 and N/A

gnomAD: N/A

Case1: GT-1, Turkish, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.2374delG heterozygous and Father: c.2374delG heterozygous

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGA2B

Variant: NM_000419.3:c.2374del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940267

gnomAD: N/A

Case12: GT-12, Caucasian, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.2326_2331dupGAGGCC and Father: deceased

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGA2B

Variant: NM_000419.3:c.957T>A and NM_000419.3:c.2326_2331dupGAGGCC

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399804780 and CA915940324

gnomAD: N/A

Case20: Patient TE, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: Article states, "heterozygous parents of TE"

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: ITGB3

Variant: NM_000212.2:c.856G>A (p.Gly286Arg) and the variant is c.1129Ains --> NM_000212.2:c.1129dup

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400020688 and CA915940291

gnomAD: MAF in the European (non-Finnish) population is 0.00001760 https://gnomad.broadinstitute.org/variant/17-45364514-G-A

Case16: Patient LN, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: Parents are heterozygous for mutation (LH and LB)

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: NM_000419.3:c.3062T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399787956

gnomAD: N/A

Case: (Patient C), Male, age, and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: 2 siblings (compound heterozygotes for the p.Cys674Arg and p.Ile374Thr mutation)

ParentalGenotype: Mother: (p.Ile374Thr) and Father: (p.Cys674Arg)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: By immunoblot analysis, it was found that the platelets of the patient and his 2 siblings contained both αIIb and β3, but at reduced levels compared with a healthy control (Figure 1B)

CasePreviousTesting: Direct sequence analysis of the of the genes encoding αIIb were performed on DNA isolated from leukocytes obtained from Patient C and family members.

Gene: ITGA2B

Variant: NM_000419.3:c.1214T>C (p.Ile405Thr) and NM_000419.3:c.2113T>C (p.Cys705Arg)

LegacyVariant: (p.Ile374Thr) and (p.Cys674Arg)

ClinVar: N/A

CAiD: CA290950815 and CA8602816

gnomAD: MAF in the European (non-Finnish) population is 0.000008792 https://gnomad.broadinstitute.org/variant/17-42455140-A-G

Case: (Patient M) Gender, age, ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia (diagnosed at 1 year old)

FamilyInfo: N/A

ParentalGenotype: Mother: (p.Val298Phe) and Father: (p.Tyr380Ter)

CasePresentingHPOs: (Went to Reference #17 to see what lab findings/phenotypes were reported for this patient; however, access not available to this article)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: By immunoblot analysis, both αIIb and β3 subunits were detected in the patient's platelet lysates, but at reduced levels compared to a healthy control and samples from both parents (Figure1A)

CasePreviousTesting: Direct sequence analysis of the of the genes encoding αIIb were performed on DNA isolated from leukocytes obtained from Patient M and family members

Gene: ITGA2B

Variant: NM_000419.3:c.985G>T (p.Val329Phe) and NM_000419.3:c.1232dup (Tyr411Ter)

LegacyVariant: (p.Val298Phe) and (p.Tyr380Ter)

ClinVar: N/A

CAiD: CA399804719 and CA915940593

gnomAD: MAF in the South Asian population is 0.0001312 https://gnomad.broadinstitute.org/variant/17-42458407-G-A

Case3: Male, age not specified, Cypriot (paternal uncle of 3 year old)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Brother and brother's daughter were also affected with same mutation (See Figure 3 for family pedigree)

ParentalGenotype: Parents were heterozygous for same mutation (See Figure 3 pedigree)

CasePresentingHPOs: HP:0000225, HP:0000421, HP:0031364

(Gingival bleeding, epistaxis, ecchymosis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed decreased surface expression of αIIb and β3 in patients' platelets

PlateletAggregation: Absent platelet aggregation in response to ADP, epineprhine, collagen but normal ristocetin induced platelet aggregation

CasePreviousTesting: SSCP analysis of the αIIb gene in the three patients revealed an altered pattern of migration of the DNA fragment containing exons 5 and 6 and their flanking intronic regions.

Gene: ITGA2B

Variant: M_000419.3:c.605T>G (p.Phe202Cys)

LegacyVariant: (p.Phe171Cys) + 31= (p.Phe202Cys)

ClinVar: N/A

CAiD: CA399805605

gnomAD: N/A

Case2: Male, age not specified, Cypriot (father of 3 year old)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Daughter and brother were also affected with same mutation (See Figure 3 for family pedigree)

ParentalGenotype: Parents were heterozygous for same mutation (See Figure 3 pedigree)

CasePresentingHPOs: HP:0000225, HP:0000421, HP:0031364

(Gingival bleeding, epistaxis, ecchymosis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed decreased surface expression of αIIb and β3 in patients' platelets

PlateletAggregation: Absent platelet aggregation in response to ADP, epineprhine, collagen but normal ristocetin induced platelet aggregation

CasePreviousTesting: SSCP analysis of the αIIb gene in the three patients revealed an altered pattern of migration of the DNA fragment containing exons 5 and 6 and their flanking intronic regions.

Gene: ITGA2B

Variant: M_000419.3:c.605T>G (p.Phe202Cys)

LegacyVariant: (p.Phe171Cys) + 31= (p.Phe202Cys)

ClinVar: N/A

CAiD: CA399805605

gnomAD: N/A

Case1: Female, 3 years old, Cypriot

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Father and paternal uncle were also affected with same mutation (See Figure 3 for family pedigree)

ParentalGenotype: Father is homozygous for the mutation and the mother is heterozygous for the mutation (See Discussion)

CasePresentingHPOs: HP:0000225, HP:0000421, HP:0031364

(Gingival bleeding, epistaxis, ecchymosis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed decreased surface expression of αIIb and β3 in patients' platelets

PlateletAggregation: Absent platelet aggregation in response to ADP, epineprhine, collagen but normal ristocetin induced platelet aggregation

CasePreviousTesting: SSCP analysis of the αIIb gene in the three patients revealed an altered pattern of migration of the DNA fragment containing exons 5 and 6 and their flanking intronic regions.

Gene: ITGA2B

Variant: NM_000419.3:c.605T>G (p.Phe202Cys)

LegacyVariant: (p.Phe171Cys) + 31= (p.Phe202Cys)

ClinVar: N/A

CAiD: CA399805605

gnomAD: N/A

Case1: Female, 20 years old, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See pedigree in Fig 2

ParentalGenotype: Parental genotype given see Fig 2

CasePresentingHPOs: HP:0000978 (Easy bruising)

CaseHPOFreeText: Mucocutaneous bleeding, menstrual hemorrhages

CaseNotHPOs: N/A

ProteinExpression: The absence of platelet GPIIb-IIIa complexes by flow cytometric analysis with MoAbs was performed and shown

Platelet Aggregation: No response detected either spontaneously or in response to agonists (this is all of the information we are given)

CasePreviousTesting: GPIIb and GPIIIa genes were screened for mutations by SSCP of PCR amplified exons from genomic DNA

Gene: ITGB3

Variant: NM_000212.2:c.1924G>T (p.Glu642Ter)

LegacyVariant: (p.Glu616Ter)

ClinVar: 13565

CAiD: CA123249

gnomAD N/A

Case2: Male, age not specified, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 3

ParentalGenotype: Both mutations were found to be heterozygous in all family members that includes parents

CasePresentingHPOs:

(Gum bleeding, ecchymosis, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed that the surface expression of GPIIb/IIIa in patients was 0% and both parents also showed reduced expression as well.

PlateletAggregation: Platelet aggregation in response to all the agonists except risocetin was completely absent in the patient

CasePreviousTesting: Mutation screening by conformational sensitive gel electrophoresis was performed in all the 30 exons of ITGA2B and 15 exons of ITGB3 gene in this patient

Gene: ITGA2B

Variant: NM_000419.3:c.1028T>C (p.Leu343Pro) and a promoter variant g.951G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399804619

gnomAD: N/A

Case1: Male, age not specified, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 3

ParentalGenotype: Both mutations were found to be heterozygous in all family members that includes parents

CasePresentingHPOs:

(Gum bleeding, ecchymosis, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed that the surface expression of GPIIb/IIIa in patients was 0% and both parents also showed reduced expression as well.

PlateletAggregation: Platelet aggregation in response to all the agonists except risocetin was completely absent in the patient

CasePreviousTesting: Mutation screening by conformational sensitive gel electrophoresis was performed in all the 30 exons of ITGA2B and 15 exons of ITGB3 gene in this patient

Gene: ITGA2B

Variant: NM_000419.3:c.1028T>C (p.Leu343Pro) and a promoter variant g.951G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399804619 and need to ask about second variant--made note in google doc to ask

gnomAD: N/A

Case1: Female, 1 year old, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000979, HP:0000421

(Purpura, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: The absence of platelet GPIIb-IIIa complexes was con-firmed by flow cytometric and immunoblotting analyses. Figure 1 shows the flow cytometric analysis of the platelets

PlateletAggregation: Absence of platelet aggregation in response to ADP, epinephrine, and collagen but the presence of a normal response to ristocetin

CasePreviousTesting: Genomic DNA was extracted by a standard protocol from the peripheral blood mononuclear cells of the patient and her parents. The flanking region of exon 25 of the GPIIb gene including the introns was amplified by PCR from the genomic DNA.

Gene: ITGA2B

Variant: NM_000419.3:c.2449-1G>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399795582

gnomAD: N/A

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: (Patient TK) Male, 5 years old, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The (p.His280Pro) mutation was inherited from his mother and the (p.Gly579Ser) mutation was inherited from his father

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients (3 in this study) had suffered from a bleeding diathesis since early childhood

CaseNotHPOs: NA

ProteinExpression: The surface expression of the alphaIIbbeta complex on the patients' platelets was quantitated by flow cytometry. The level of antigen expression for TK was 19.9%

Platelet Aggregation: Absent platelet aggregation in response to ADP, collagen, and epinephrine, but normal platelet agglutination in response to ristocetin

CasePreviousTesting: The nucleotide sequences of the aIIb and b3 coding regions were determined by direct sequencing of RT-PCR products from platelet RNA

Gene: ITGB3

Variant: NM_000212.2:c.917A>C (p.His206Pro) and NM_000212.2:c.1813G>A (p.Gly605Ser) (See Table 1 to see zygosity statement, "double heterozygote for both variants")

LegacyVariant: (p.His280Pro) and (p.Gly579Ser)

ClinVar: N/A

CAiD: CA291224999 and CA291227621

gnomAD MAF in the East Asian population for (p.His206Pro) is 0.00005437 https://gnomad.broadinstitute.org/variant/17-45364575-A-C and MAF in East Asian population for (p.Gly605Ser) is 0.00005437 https://gnomad.broadinstitute.org/variant/17-45376796-G-A

Case2: 6 year old, Female, Chinese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Case1 is sister of this proband. Additional family information found in table 1.

ParentalGenotype: Father: Heterozygous for the p.Cys549Ser variant and did not find the p.Gln254Lys variant. Mother: Did not find the p.Cys549Ser variant but she is heterozygous for the p.Gln254Lys variant.

CasePresentingHPOs: HP:0002248

CaseHPOFreeText: Upper gastrointestinal bleeding added up to five times at age 2.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: The expression of CD41 and CD61 was detected by platelet immunofluorescence test-flow cytometry. The expression of CD41 and CD61 of Case1 was remarkably lower than other family members (261.90 and 355.45 respectively).

CasePreviousTesting: DNA was isolated and ITGB3 and ITGA2B gene sequences were amplified by PCR with a high fidelity Taq Polymerase.

Gene: ITGB3

Variant: NM_000212.2:c.1646G>C (p.Cys549Ser), and NM_000212.2:c.760C>A (p.Gln254Lys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400030198 (p.Cys549Ser) and CA400023674 (p. Gln254Lys)

gnomAD: MAF: 0.00005453 (p.Cys549Ser) https://gnomad.broadinstitute.org/variant/17-45369890-G-C and MAF not available for (p.Gln254Lys)

Case1: 5 year old, Female, Chinese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Case2 is the sister of this proband, additional family information found in Table 1

ParentalGenotype: Father: Did not find the p.Cys549Ser variant and is heterozygous for p.Leu705CysfsTer4 variant. Mother: Heterozygous for the p.Cys549Ser variant and did not find the p.Leu705CysfsTer4 variant.

CasePresentingHPOs: HP:0004406, HP:0000790

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: The expression of CD41 and CD61 was detected by platelet immunofluorescence test-flow cytometry. The expression of CD41 and CD61 of Case1 was remarkably lower than other family members (261.90 and 355.45 respectively).

CasePreviousTesting: DNA was isolated according to the manufacturer's instruction-- ITGA2B and ITGB3 gene sequences were amplified by PCR with a high fidelity TAQ Polymerase.

Gene: ITGB3

Variant: NM_000212.2:c.1646G>C (p.Cys549Ser), and NM_000212.2:c.2113del (p.Leu705CysfsTer4)

LegacyVariant: N/A

ClinVar: Not available for either of the two variants.

CAiD: CA400030198 (p.Cys549Ser), CA8623443 (p.Leu705CysfsTer4)

gnomAD: MAF: 0.00005453 (p.Cys549Ser) https://gnomad.broadinstitute.org/variant/17-45369890-G-C and MAF: 0.0001087 (p.Leu705CysfsTer4) https://gnomad.broadinstitute.org/variant/17-45380183-TC-T

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

Case1: (M.S) Female, 19 years old, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The mutation has been inherited from proband's parents who are heterozygous for the same mutation the proband has.

CasePresentingHPOs: HP:0000978 (Bruising)

CaseHPOFreeText: Intracerebral hematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Fig 4 for flow cytometry analysis of protein expression

PlateletAggregation: Absence of platelet aggregation in response to all agonists tested i.e. ADP, collagen, platelet activating factor acether thrombin, and arachidonic acid; however, ristocetin induced platelet aggregation was normal

CasePreviousTesting: Sequenced patient's GPIIIa exons encompasing a highlight conserved reion of GPIIIa.

Gene: ITGB3

Variant: NM_000212.2:c.718C>T (p.Arg240Trp)

LegacyVariant: (p.Arg214Trp)

ClinVar: 13555

CAiD: CA123228

gnomAD: MAF in the East Asian population is 0.00005437 http://gnomad.broadinstitute.org/variant/17-45363729-C-T

PreviouslyPublished: PMID: 1602006

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

Case1: Female, 22 years old, Portugese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Also studied were the patient’s mother (I.2),her father (1.1), and her sister (II.2). Of these family members, only her sister has reported excessive bleeding although platelet aggregation tests were normal for all of them. Consanguinity was present as her parents were cousins.

ParentalGenotype: Parents heterozygous for mutation

CasePresentingHPOs: HP:0000967

(Petechia)

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: <5% surface expression of aIIbb3

PlateletAggregation: Absent with physiologic agonists but agglutination with ristocetin was normal

CasePreviousTesting: We examined each of the 30 exons of the b3 gene and each of the 15 exons of the aIIb gene for migration changes in PCR-SSCP analysis

Gene: ITGB3

Variant:

LegacyVariant:

ClinVar:

CAiD:

gnomAD: N/A

Case1: Female, 5 years old, South East Asian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Information given on paternal grandmother

ParentalGenotype: Article mentions that NM_000419.3:c.1946+1G>A was of maternal inheritance and NM_000419.3:c.2944G>A (Val951Met) and NM_000419.3:c.2965G>A (p.Ala958Thr) is of paternal inheritance giving triple heterozygosity

CasePresentingHPOs: HP:0000978, HP:0000421

(Severe bruising, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Flow cytometry showed an ∼4% residual surface expression of αIIbβ

PlateletAggregation: No aggregation in response to ADP, epinephrine or arachidonic acid but a small residual response to collagen

CasePreviousTesting: Extraction of genomic DNA was done and PCR amplification of DNA fragments corresponding to each of the 30 exons in ITGA2B and 15 exons of ITGB3 and SSCP analysis were all performed

Gene: ITGA2B

Variant: NM_000419.3:c.2944G>A (p.Val982Met) and NM_000419.3:c.2965G>A (p.Ala989Thr) and NM_000419.3:c.1946+1G>A

LegacyVariant: (p.Val951Met) and (p.Ala958Thr)

ClinVar: 381747 and 417951 and 569057

CAiD: CA16608466 and CA8602498 and CA8602901

gnomAD: MAF in the Europmean (non-Finnish) population is 0.00006486 https://gnomad.broadinstitute.org/variant/17-42451838-C-T and MAF in the Other population is 0.001939 https://gnomad.broadinstitute.org/variant/17-42451817-C-T and MAF in the East Asian population is 0.00007555 https://gnomad.broadinstitute.org/variant/17-42456010-C-T

Case1: Male, 5 years old, Swiss

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Family pedigree provided in Figure 1- blood samples for the study were obtained from the patient, his parents and 5 other members of his family and none of the other studied family members have experienced abnormal bleeding

ParentalGenotype: Studied and no mutation detected

CasePresentingHPOs: N/A

CaseHPOFreeText: Frequent mucocutaneous bleeding with transfusion being required shortly after birth

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: <2% of the normal platelet content of GPIIb-IIIa as determined by flow cytometry

PlateletAggregation: Absence of platelet aggregation in response to ADP, epinephrine, thrombin and collagen; however, normal platelet agglutination with ristocetin

CasePreviousTesting: Using a PCR‐SSCP procedure and direct sequence analysis of PCR‐amplified DNA fragments, we have examined all exons and splice sites of the GPIIb and GPIIIa genes

Gene: ITGA2B

Variant: NM_000419.3:c.1063G>A (p.Glu355Lys) and NM_000419.3:c.1787T>C (p.Ile596Thr)

LegacyVariant: (p.Glu324Lys) and (p.Ile565Thr)

ClinVar: 2899 and 2900, respectively

CAiD: CA115844 and CA115846, respectively

gnomAD: MAF in the European (non-Finnish) population is 0.00001978 https://gnomad.broadinstitute.org/variant/17-42461008-C-T and the MAF in the European (non-Finnish) population is 0.0001325 https://gnomad.broadinstitute.org/variant/17-42457148-A-G

Case1: Gender or age not specified, Thai ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Father: p.Arg584Ter/WT and Mother: p.Leu973Alafs*63/WT (See Table 2)

Note: No parental consanguinity

CasePresentingHPOs: N/A

CaseHPOFreeText: The article does not mention specific bleeding phenotypes for each of the 4 probands in the article, rather, there is a general statement that says: "The common presentations included recurrent epistaxis, bleeding in oral cavity, and easy-bruising spontaneously or after trauma"

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinEpression: General statement from the article that states that flow cytometry to assess the surface GPIIb/IIIa complex showed reduced expression for all probands.

PlateletAggregation: The platelet aggregation test was typically defective with all physiological agonists except ristocetin, for all patients.

CasePreviousTesting: Whole exome sequencing was performed on the 30 exons of ITGA2B and 15 exons in ITGB3. PCR and direct sequencing were then performed in the DNA samples of the patients and their available parents to verify the presence of the identified mutations.

Gene: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) and NM_000419.3:c.2915dup (p.Leu973Alafs*63)

LegacyVariant: N/A

ClinVar: 2892 (p.Arg584Ter)

CAiD: CA115834 (p.Arg584Ter) and CA8602531 (p.Leu973Alafs*63)

gnomAD: MAF for (p.Arg584Ter) in the East Asian population 0.0002176 http://gnomad.broadinstitute.org/variant/17-42457372-G-A and MAF for (p.Leu973Alafs*63) in the East Asian population 0.0001088 http://gnomad.broadinstitute.org/variant/17-42452054-C-CG

Case4: Gender or age not specified, Thai ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Parental information available in Table 2

ParentalGenotype: Father: p.Gln508Hisfs*3/WT and Mother: No mutations in the coding region

Note: No parental consanguinity

CasePresentingHPOs: N/A

CaseHPOFreeText: The article does not mention specific bleeding phenotypes for each of the 4 probands in the article, rather, there is a general statement that says: "The common presentations included recurrent epistaxis, bleeding in oral cavity, and easy-bruising spontaneously or after trauma"

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinEpression: General statement from the article that states that flow cytometry to assess the surface GPIIb/IIIa complex showed reduced expression for all probands.

PlateletAggregation: The platelet aggregation test was typically defective with all physiological agonists except ristocetin, for all patients.

CasePreviousTesting: Whole exome sequencing was performed on the 30 exons of ITGA2B and 15 exons in ITGB3. PCR and direct sequencing were then performed in the DNA samples of the patients and their available parents to verify the presence of the identified mutations.

Gene: ITGA2B

Variant: NM_000419.3:c.1524_1533del (p.Gln508Hisfs*3)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940265

gnomAD: N/A

Case2: Gender or age not specified, Thai ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Parental information available in Table 2

ParentalGenotype: Father: p.Val206Asp/WT and Mother: also p.Val206Asp/WT (See Table 2)

Note: Yes to parental consanguinity

CasePresentingHPOs: N/A

CaseHPOFreeText: The article does not mention specific bleeding phenotypes for each of the 4 probands in the article, rather, there is a general statement that says: "The common presentations included recurrent epistaxis, bleeding in oral cavity, and easy-bruising spontaneously or after trauma"

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinEpression: General statement from the article that states that flow cytometry to assess the surface GPIIb/IIIa complex showed reduced expression for all probands.

PlateletAggregation: The platelet aggregation test was typically defective with all physiological agonists except ristocetin, for all patients.

CasePreviousTesting: Whole exome sequencing was performed on the 30 exons of ITGA2B and 15 exons in ITGB3. PCR and direct sequencing were then performed in the DNA samples of the patients and their available parents to verify the presence of the identified mutations.

Gene: ITGA2B

Variant: NM_000419.3:c.617T>A (p.Val206Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805578

gnomAD: N/A

Case1: Female, 22 years old, Portuguese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Also studied were the probands mother (I.2) father (1.1) and sister (II.2) and only her sister has reported excessive bleeding, although her platelet aggregation tests were normal for all of them (See Fig. 2A)

ParentalGenotype: Parents were heterozygous

CasePresentingHPOs: HP:0000967

(Petechia)

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Western blot expression study shows classic type 1 GT with less than 5% surface expression of aIIb3

PlateletAggregation: Platelet aggregation was absent with physiological agonists but agglutination with ristocetin was normal

CasePreviousTesting: Examined each of the 30 exons of beta3 gene and each of the 15 exons of the aIIb gene for migration changes in PCR-SSCP analysis. Each PCR reaction was controlled by electrophoresis of the amplified fragments on 1.5% agarose gels

Gene: ITGB3

Variant: NM_000212.2:c.1924G>T (p.Glu642Ter)

LegacyVariant: N/A

ClinVar: 13565

CAiD: CA123249

gnomAD: N/A

Case3: Patient F3P1, Male, 26 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Table 1 states there is a family history of bleeding (we have minimal to no specific info on this)

ParentalGenotype: Mother and father are heterozygous for this mutation

CasePresentingHPOs: HP:0000225, HP:0004406, HP:0000978,HP:0000790, HP:0002239

(Gingival bleeding, recurrent epistaxis, easy bruising, hematuria, GI bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: GT diagnosis was based on absent platelet aggregation induced by ADP, collagen, and TRAP and subnormal or cyclical ristocetin induced agglutination

CasePreviousTesting: Using PCR they successfully amplified 20 DNA fragments for the ITGA2B gene (covering more than 48% of the ITGA2B gene constituting 30 exons) and15 DNA fragments of theITGB3gene (covering 15 exons)

Gene: ITGA2B

Variant: NM_000419.3:c.2702C>A (p.Ser901X) another variant this patient has is g.13944G>A --> I am noting this as Unknown Variant as I will need guidance curating this one

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399792888

gnomAD: N/A

Case1: Patient F1P1, Male, 11 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Table 1 states there is a family history of bleeding (we have minimal to no specific info on this)

ParentalGenotype: Mother and father are heterozygous for mutation

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: GT diagnosis was based on absent platelet aggregation induced by ADP, collagen, and TRAP and subnormal or cyclical ristocetin induced agglutination

CasePreviousTesting: Using PCR they successfully amplified 20 DNA fragments for the ITGA2B gene (covering more than 48% of the ITGA2B gene constituting 30 exons) and15 DNA fragments of theITGB3gene (covering 15 exons)

Gene: ITGA2B

Variant: NM_000419.3:c.2702C>A (p.Ser901X) another variant this patient has is g.13944G>A --> I am noting this as Unknown Variant as I will need guidance curating this one

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399792888

gnomAD: N/A

Case2: Patient F2P1, Male, 34 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Table 1 states there is a family history of bleeding (we have minimal to no specific info on this)

ParentalGenotype: Mother and father are heterozygotes for the mutation here

CasePresentingHPOs, : HP:0000225, HP:0004406, HP:0000978,HP:0000790

(Gingival bleeding, recurrent epistaxis, easy bruising, hematuria)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: GT diagnosis was based on absent platelet aggregation induced by ADP, collagen, and TRAP and subnormal or cyclical ristocetin induced agglutination

CasePreviousTesting: Using PCR they successfully amplified 20 DNA fragments for the ITGA2B gene (covering more than 48% of the ITGA2B gene constituting 30 exons) and15 DNA fragments of theITGB3gene (covering 15 exons)

Gene: ITGA2B

Variant: NM_000419.3:c.2702C>A (p.Ser901X) another variant this patient has is g.13944G>A --> I am noting this as Unknown Variant as I will need guidance curating this one

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399792888

gnomAD: N/A

Case1: Female, 35 years old, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Pedigree found in Fig 4

ParentalGenotype: Mother: heterozygote for (p.Ile330Asn) and Father: heterozygote for (p.His306Pro)

CasePresentingHPOs: N/A

CaseHPOFreeText: Profuse bleeding at times

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: The surface expression of αIIbβ3 complex on the patient's platelets was not observed in the flow cytometric analysis used to detect the αIIbβ3 complex (Fig. 1A).

PlateletAggregation: No aggregation of patient's platelets in response to ADP and collagen but normal aggregation occurred in response to ristocetin

CasePreviousTesting: Nucleotide sequences of beta3 cDNA and beta3 genomic DNA were analyzed by the dye terminator cycle sequencing method, in addition the nucleotide sequences of alphaIIbeta cDNA were anlso analyzed based on the published sequence of alphaIIbeta

Gene: ITGB3

Variant: NM_000212.2:c.989T>A (p.Ile330Asn) and NM_000212.2:c.917A>C (p.His306Pro)

LegacyVariant: (p.Ile304Asn) and (p.His280Pro)

ClinVar: N/A

CAiD: CA400025722 and CA291224999

gnomAD: MAF in the East Asian population is 0.00005437 https://gnomad.broadinstitute.org/variant/17-45364575-A-C

Case1: V.17, Male, French (Gypsy), age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Pedigree shown in Fig 1

ParentalGenotype: Mother and father are heterozygous for the mutation

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The alphaIIb full length cDNA of this patient were amplified by PCR

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case1: Male, 14 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Parents were heterozygous for the variant of interest

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0031364

(Epistaxis, gingival bleeding, ecchymosis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: The proband's platelets did not express GPIIb and small amounts of GPIIIa were detected.

PlateletAggregation: Absence of platelet aggregation after stimulation by ADP, collagen, and thrombin. Ristocetin-induced platelet agglutination was normal

CasePreviousTesting: Exon 26 of the GPIIb gene was amplified by PCR with primers

Gene: ITGA2B

Variant: NM_000419.3:c.2702C>A (p.Ser901Ter)

LegacyVariant: (p.Ser870Ter)

ClinVar: N/A

CAiD: CA399792888

gnomAD: N/A

Case1: Female, 22 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 1

ParentalGenotype: The patient's parents revealed reduced concentrations of glycoprotein llb-Illa and were considered to be heterozygotes. See Fig 1

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132, HP:0000978

(Severe epistaxis, gingival bleeding, menorrhagia, spontaneous bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Platelets had much reduced alphaIIb3 when estimated by crossed immunoelectrophoresis

PlateletAggregation: Platelet aggregation was absent with ADP, arachidonic acid, and collagen.

CasePreviousTesting: Sequenced all exons and splice sites of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1073G>A (p.Arg358His) and NM_000419.3:c.1234G>A (p.Gly412Arg)

LegacyVariant: (p.Arg327His) and (p.Gly381Arg)

ClinVar: 2896 and 381748

CAiD: CA115839 and CA8603182

gnomAD: MAF in the Latino population is 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T

PreviouslyPublished: PMID: 3762006 proband is mentioned in this article

Case1: Female, 5 years old, Swiss (from Morocco)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother

ParentalGenotype: Mother and father are heterozygous for the variant of interest

CasePresentingHPOs: HP:0001250, HP:0001270, HP:0000967, HP:0001892

(Seizures, retarded motor development, petechia, hemorrhagic diathesis)

CaseHPOFreeText: Subepndymal hematomas, cortical tubera, hydrocephalus internus

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry protein expression results can be seen in Figure 1

PlateletAggregation: Platelets failed to aggregate with ADP, collagen, or arachidonic acid; however, ristocetin induced platelet agglutination was normal

CasePreviousTesting: Amplified DNA fragments containing exon 11 of the GPIIIa gene were purified by PCR preps DNA purification resin and wizard.

Gene: ITGB3

Variant: NM_000212.2:c.1702T>C (p.Cys568Arg)

LegacyVariant: (p.Cys542Arg)

ClinVar: N/A

CAiD: CA400032350

gnomAD: N/A

Case2: Female, 28 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: N/A

ParentalGenotype: Parents were heterozygous for this mutation and did not show bleeding symptoms

Note: There is parental consanguinity

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe haemorrhagia and haematomas associated with prolonged in vivo bleeding time

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis revealed 3.5 % of αIIbβ3 was detected on the platelet surface from patient 2.

PlateletAggregation: Article states agonist-induced platelet aggregation and binding of exogenous fibrinogen was pathological, too but does not mention specific agonists used or response to ristocetin

CasePreviousTesting: Molecular genetic analysis was done; however, no other information mentioned. In addition, the global proteome of highlight purified washed platelets was quantified by liquid chromatography-mass spectrometry and targeted MS-methods.

Gene: ITGA2B

Variant: NM_000419.3:c.2374del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940267

gnomAD: N/A

Case1: Male, 14 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: Sister is also heterozygous for this mutation but shows no bleeding symptoms

ParentalGenotype: Both parents are heterozygous for this mutation

Note: There is parental consanguinity

CasePresentingHPOs: HP:0000967, HP:0000225, HP:0000421

(Petechiae, ginigival bleeding, epistaxis)

CaseHPOFreeText: Haematoma,

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis revealed 3.8 % platelet surface presentation of the αIIbβ3 complex for patient 1 and αIIb was not detected and β3 was significantly reduced in Western blots. Platelets from GT patients showed less than 5 % relative levels of the integrin subunit IIb and 5–9 % fibrinogen compared to controls.

PlateletAggregation: Article states agonist-induced platelet aggregation and binding of exogenous fibrinogen was pathological, too but does not mention specific agonists used or response to ristocetin

CasePreviousTesting: Molecular genetic analysis was done; however, no other information mentioned. In addition, the global proteome of highlight purified washed platelets was quantified by liquid chromatography-mass spectrometry and targeted MS-methods.

Gene: ITGA2B

Variant: NM_000419.3:c.175del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940266

gnomAD: N/A

Case1: (Patient LD) Female, 3 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 4 for family pedigree

ParentalGenotype: Father is heterozygous for GC867-G and Mother is heterozygous for T882C (See Fig 4)

CasePresentingHPOs: HP:0000967, HP:0031364, HP:0000978, HP:0000225

(Petechiae, ecchymosis, bruising, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Fig 2A shows reduced expression (See Fig2A)

PlateletAggregation: Platelets did not aggregate in response to ADP, epinephrine, or arachidonic acid and showed only shape change in response to collagen. Platelets did agglutinate with ristocetin.

CasePreviousTesting: Genomic DNA was prepared from peripheral blood leukocytes and amplified by polymerase chain reaction (PCR) with Taq polymerase by using oligonucleotide primers from intronic flanking sequences of αIIb and β3. All exons of both genes were sequenced at least twice to exclude Taq errors.

Gene: ITGB3

Variant: NM_000212.2:c.863T>C (p.Leu288Pro) and NM_000212.2:c.847_848del

LegacyVariant: (p.Leu262Pro)

ClinVar: N/A

CAiD: CA400024958 and CA8623068

gnomAD: for c.847_848del https://gnomad.broadinstitute.org/variant/17-45364504-AGC-A

Case1: (Patient JO) Female, 38 years old, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Parents shown Fig 6

CasePresentingHPOs: HP:0000978, HP:000042, HP:0000132

(Easy bruising, epistaxis, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Figure 6 shows surface expression

Platelet Aggregation: Absent aggregation in response to ADP, epinephrine, collagen and thrombin however normal response to ristocetin

CasePreviousTesting: Total cellular RNA was obtained, and aIIbb3 mRNAs were specifically amplified by reverse transcription PCR (RT-PCR) as previously described (41).

Gene: ITGA2B

Variant: NM_000419.3:c.575_576insGGACAA (went over with Shruthi)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940650

gnomAD N/A

Case1: Male, 9 years old,

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: One brother, with no signs of bleeding diathesis

ParentalGenotype: Father is heterozygous for the c.2268C>T mutation and the mother is compound heterozygous with the c.2268C>T variant and c.2330C>T variant

CasePresentingHPOs: HP:0000421 Epistaxis

CaseHPOFreeText: Submucosal bleeding, hematomas, excessive achilles tendon bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: The patient's αIIbβ3 receptor count was estimated approximately 50% of that measured in a healthy age-matched control by quantitative flow cytometry

PlateletAggregation: Complete absense of platelet aggregation in response to ADP, arachidonic acid, epinephrine, collagen

CasePreviousTesting: Direct sequencing of the patients αIIb and β3 genes was perforemed

Gene: ITGB3

Variant: NM_000212.2:c.2248C>T (p.Arg750Ter)

LegacyVariant: (p.Arg724Ter)

ClinVar: 13564

CAiD: CA123246 (p.Arg750Ter)

gnomAD: N/A