Case#: Peretz_1995_proband. 26 y.o. female. Iranian-Jewish

DiseaseAssertion: Glanzmann's Thrombasthenia

FamilyInfo: consanguineous, 1 of 2 brothers were affected (affected was homozygous for variant, unaffected was homozygous for normal, both siblings with no platelet aggregation with ADP, collagen, epinephrine, and normal response to ristocetin. Their clot retraction was absent and the binding of monoclonal antibody (MoAb) 10E5, which recognizes the GPIIb/IIIa complex,26 was minimal.

ParentalGenotype: heterozygous, both

CasePresentingHPOs:

PlateletAggregation: no platelet aggregation in response to adenosine diphosphate, collagen, or epinephrine and had a normal response to ristocetin.

CaseHPOFreeText: moderate mucocutaneous bleeding

CaseNotHPOs:

CaseNotHPOFreeText:

ProteinExpression: heterodimer in transfected COS-7 cells resulted in low peroxidase activity, indicating lack of surface expression of the heterodimer.

CasePreviousTesting:

Method: Testing was through southern blot analysis with restriction enzymes and amplification of fragments

PreviouslyPublished:

Gene: ITGA2B

Variant: 6-bp deletion and 31-bp insertion in exon 25 of the GPIIb gene - altered C-terminal sequence of 105 amino acids starting at Val-825 - substitution of 10 amino acids Leu817-Asn826 by an altered sequence of 8 amino acids

HGVS: NM_000419.5:c.2473_2478delinsTCACCAGGGCCTTCACGTGAGCATGGAGAG

ClinVar:

CAID: CA2581931358

gnomAD: No matching variants found

Case#: Basani_1996_LeM, female, Caucasian, >1 y.o.

DiseaseAssertion: GT

FamilyInfo: nonconsanguineous parents

ParentalGenotype: one obligatory carrier

CasePresentingHPOs: HP:0000967 Petechiae, HP:0000979 Purpura,

PlateletAggregation: absence of platelet aggregation in response to adenosine diphosphate (ADP), epinephrine, and collagen, but a normal response to ristocetin.

CaseHPOFreeText: Platelet Count (1 day old): 181,000/mm^3

CaseNotHPOs:

CaseNotHPOFreeText:

ProteinExpression: Flow cytometry: platelets expressed <5% of the normal amount of αIIbβ3 when stained with the β3-specific MoAb SSA6,24 the heterodimer-dependent MoAb A2A923,24 or the activation-dependent MoAb PAC1.25 On the other hand, LeM and control platelets bound comparable amounts of the anti-GPIb MoAb AP1, confirming that the defect in the patient's platelets was confined to αIIbβ3

CasePreviousTesting:

Method: PCR using VENT polymerase confirmed with SSCPA

PreviouslyPublished:

Gene: ITGA2B

Variant: exon 13 sequence containing the 6 bp deletion 5’-GTGACA-3’ (deletion of Val425-Asp426) (heterozygous)

HGVS: NM_000419.5:c.1366_1371del (p.Val456_Asp457del)

ClinVar: 2898

CAID: CA8603160

gnomAD: 0.000008791 European (non-Finnish)

Case#: a 12-year-old female admitted to the B Department Hédi Raies institut of Ophtalmology in Tunis, Tunisia

DiseaseAssertion: Cone rod dystrophy

FamilyInfo: No parental consanguinity nor pathological or opthalmological history in the family

CasePresentingHPOs: HP:0000529, HP:0000662, HP:0001141, HP:0000543,HP:0007737, HP:0030602

CaseHPOFreeText: progressive visual loss, poor night vision, 1/20 visual acuity in both eyes, pallor of the optic disk, attenuated retinal vessels, paravascular bone spiculed pigmentations and an epimacular membrane, paravascular and macular heterogeneous hypoautofluorescence, diffuse alteration of ellipsoid zone, decreased photopic and scotopic responses.

CaseNotHPOs: NR

CaseNotHPOFreeText: NR

Genotyping Method: Whole exome sequencing, Sanger sequencing

PreviouslyPublished: NR

Variant: c.885delC, NM_000350.3

ClinVar: 438109

CAID: CA958684

SupplementalData: Karyotyping showed monosomy 45,X in the patient