Recurrent Mutations of Factor XI Gene in Japanese

Abstract

Factor XI (FXI) deficiency is most commonly found in individuals of Ashkenazi Jewish origin and consists of a splice-junction abnormality (type I), a nonsense mutation in exon 5 (type II), or a missense mutation in exon 9 (type III) [1,2]. However, it has also been reported in other ethnic populations, including Japanese, as a rare bleeding disorder inherited as an autosomal recessive condition, and it is often diagnosed following abnormal bleeding after trauma or surgical operation [3]. In the present study, we investigated the molecular basis of FXI deficiency in Japanese patients under ethical approval from the Ethics Committee of Nagoya University School of Medicine. Direct sequencing of polymerase chain reaction (PCR) products specific for the FXI gene revealed 4 distinct and potentially causative mutations in 5 unrelated Japanese patients with FXI deficiency (Table 1). Although 81 mutations associated with FXI deficiency have been reported to date [1], we found a novel mutation, C773T (Gln226Stop) in exon 7, and 3 previously reported mutations in unrelated Japanese subjects: 2 missense mutations (G1296T [Gly400Val] and T759C [Phe221Ser]), and a G to A transition at position +1 at the exon 10 splicing donor site (exon 10 +1 G→A). C773T was identified in case 1 as a homozygous mutation and in case 2 as a heterozygous mutation. In case 2,The other FXI gene mutation, G1296T, was found to be heterozygous in case 2 and homozygous in case 3. T759C in case 4 was a homozygous mutation, and exon 10 +1 G→A was detected in case 5 as a heterozygous mutation. These FXI gene abnormalities were confirmed by PCR–restriction fragment length Recurrent Mutations of Factor XI Gene in Japanese