Case#: 8, male

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: Proband's mother and sister are confirmed carriers of hemophilia

ParentalTesting: Mother was tested and found to be a carrier of hemophilia

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 40%, FVIII:Ag = 25%, assay discrepancy present (OSA>CSA)

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: For exons 1–13 and 15–26, PCR primers were designed for denaturing gradient gel electrophoresis (DGGE) and exon 14 was amplified in four overlapping fragments and subsequently sequenced. VWF:Ag was tested and found to be within normal ranges.

Gene: F8

Variant: NM_000132.3:c.694A>T

LegacyVariant:

ClinVar: No

CAID: CA414919124

gnomAD:

Case#: Patient B (assumed male)

DiseaseAssertion: Moderate, Sporadic Hemophilia B

FamilyInfo: Patient B is deceased and only a DNA sample was available; his two sisters and mother are carriers

ParentalTesting: Mother was heterozygous for the variant

CasePresentingHPOs: None

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Gln)

LegacyVariant: c.6365 G>A (p.Arg-4Gln)

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Patient D (assumed male)

DiseaseAssertion: Severe, Sporadic Hemophilia B

FamilyInfo: Patient D's mother is heterozygous and she has had a second, affected son. the maternal grandmother's DNA was also heterozygous

ParentalTesting: Mother was heterozygous for the variant

CasePresentingHPOs: HP:0011858

CasePresentingHPOsFreeText: reduced factor IX activity (FIX:C: <1; FIX:Ag:41)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Gln)

LegacyVariant: c.6365 G>A (p.Arg-4Gln)

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Patient A (assumed male)

DiseaseAssertion: Moderate, Familial Hemophilia B

FamilyInfo: Mother and two sisters were heterozygous for the CG to CA transition; One sister’s prenatal sample was hemizygous for absence of cleavage indicating an affected male, confirmed after birth.

ParentalTesting: Mother was heterozygous for the variant

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C: 2 FIX:Ag: 40)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Gln)

LegacyVariant: c.6365 G>A (p.Arg-4Gln)

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Patient C (assumed male)

DiseaseAssertion: Severe, Sporadic Hemophilia B

FamilyInfo: Patient C's mother and two sisters were also heterozygous; and the third sister was homozygous for cleavage and is a non-carrier

ParentalTesting: Mother was heterozygous for the variant

CasePresentingHPOs: HP:0011858

CasePresentingHPOsFreeText: reduced factor IX activity (FIX:C: <1; FIX:Ag:65)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Gln)

LegacyVariant: c.6365 G>A (p.Arg-4Gln)

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Taipei_1 & Taipei_2 (assumed male; Chinese)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: Mothers of both families were found to be carriers as well as several other females in the family

ParentalTesting: Mothers were carriers

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (Patient 1: FIX:C: <1% FIX:Ag: 38 ; Patient 2: FIX:C: <1% ; FIX:Ag: 55)

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Gln)

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Enayat_Family 7

DiseaseAssertion: Severe Hemophilia B (Familial; from Shiraz, Iran)

FamilyInfo: Affected mothers and some sisters were investigated as the "family"

ParentalTesting:

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C: < 0.01)

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Gln)

LegacyVariant: c.6365 G>A (p.Arg-4Gln)

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: HBF12 (North Indian origin)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: For each patient at least two first or second degree relatives were also analyzed. In every case the mother of the patient was analyzed to establish the presence of the mutation in the heterozygous state.

ParentalTesting: Mother

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant:NM_000133.4:c.127C>T (p.Arg43Trp)

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: P5 (female)

DiseaseAssertion: Carrier

FamilyInfo: N/A

ParentalTesting: Investigation found that large gene defect was not found in the patient P5's mother and grandmother

CasePresentingHPOs: HP:0003125, HP:0001928, HP:0001892

CaseHPOFreeText: Low FVIII levels (FVIII:C levels were significantly decreased compared to the WT (13.4% ± 0.8, P < 0.01); FVIII:Ag levels were normal both in the conditioned media and cell lysate (respectively 90.7% ± 6.3 and 109.0% ± 9.5)), abnormal blood coagulation, mild bleeding tendency, haematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection and in silico analysis were also performed.

Gene: F8

Variant: NM_000132.4:c.2044G>C

CAID: CA414909252

gnomAD: Absent/Not Reported