LAUSR

Sir, Hemophilia A (HA) is the most common Xlinked bleeding disorder caused by absent, reduced, or dysfunction of factor FVIII coagulant activity (FVIII:C) due to mutations in the F8 gene. In mild/ moderate hemophilia A (MHA), bleeding occurs after trauma or surgery.1 F8 gene is located on the X chromosome, comprising 26 exons. F8 is translated into a 2351amino acid polypeptide containing a 19amino acid signal peptide, which will be cleaved to produce a 2332amino acid multidomain glycoprotein composed of 3 Atype domains, 1 B domain, 2 Ctype domains, and 3 small acidic atype regions (A1a1A2a2Ba3A3C1C2). The mature heterodimer FVIII is produced after intracellular cleavage, which is composed of 3 A domains homologous to a Copper binding protein ceruloplasmin, 2 C domains homologous to coagulation FV, and 1 B domain without any known homology. FVIII is released from VWF after specific proteolysis by thrombin, formed of heterotrimer activated FVIII (A1A2A3C1C2). The mutation spectrum of F8 gene is complex, including intron22/1 inversions, large segmental deletions spanning several exons, single nucleotide mutation, and total deletion due to chromosomal structural rearrangements. Many mutations have been included in HGMD (www.hgmd.cf.ac.uk) and EAHAD (www.factorviii-db.org) databases. More than 2703 mutations responsible for HA have been identified, and FVIII p.Arg1800His (Legacy Arg1781His) has been widely reported in patients with MHA in Caucasian population, but seldom identified in Asian population except for a patient in Taiwan.2-6 Herein, two families with MHA patients were studied. Hemizygous FVIII p.Arg1800His mutation was found in all included MHA patients, but these patients showed varied FVIII:C and phenotype, suggesting variable expressivity. This is the first report of FVIII p.Arg1800His mutation in China mainland.