Investigation of discordant phenotype in mild Hemophilia A using whole exome sequencing

Prothrombotic variants as modifiers of clinical phenotype in four related individuals with haemophilia A

“…To identify additional variants that may modify clinical phenotype, we employed a targeted approach, focusing on 140 genes associated with monogenic bleeding disorders or impacting FVIII levels (Table S1). 7,8 This revealed 748 variants present in at least one of the subjects (Table S2).…”

“…14 More recently, R2 is proposed to ameliorate bleeding phenotypes in an asymptomatic male with mild FVIII deficiency. 7 A strong candidate variant to reduce bleeding sequela is rs35335161 within the VWF gene. 15 This SNV results in a Phe2561Tyr alteration and resides in the C4 domain of VWF that is involved in platelet binding.…”