A factor XI deficiency associated with a nonsense mutation (Trp501stop) inthe catalytic domain

We identified a novel mutation in an asymptomatic 65-year-old Japanese man with severe factor XI deficiency. Sequence analysis after polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP) analysis of h is factor XI gene revealed a G -->A transition in codon 501 of exon 13, res ulting in a substitution of Trp501 (T (G) under barG) by a stop codon (T (A ) under barG) in the catalytic domain. This mutation abolished a FokI restr iction site. The PCR product from normal subjects was digested with FokI an d yielded two fragments, one of 223 bp and one of 47 bp. The PCR product fr om the patient gave a single 270-bp fragment, demonstrating possible homozy gosity.