Hemizygous F8 p.G201E mutation identified in a Chinese family with haemophilia A.

Abstract

Haemophilia A (HA), inherited via an X-linked recessive pattern, is the most common severe lifelong bleeding disorder caused by mutations in the coagulation factor VIII gene (F8). It has significant socio-economic effects due to its long course of disease and high cost of care. These impacts argue for a more accurate genetic diagnosis in an increasingly complex clinical environment. A three-generation Han-Chinese family with mild HA was recruited in the study. Exome sequencing was performed in the index case to detect potential disease-causing mutations, and Sanger sequencing was applied to verify the mutation in the family. A hemizygous c.602G > A variant in the F8 gene, leading to a single amino acid substitution at codon 201 from glycine to glutamic acid (p.G201E) within the factor VIII (FVIII) A1 domain, was identified in the HA family. This mutation detected in the proband was found in his affected sibling, while it was absent in the unaffected family member and the two hundred ethnically-matched controls. The mutation affects an evolutionary conserved residue, which may impact the tertiary structure of FVIII. The study findings should provide for more dependable and precise genetic counseling which may assist in perfecting family management.