Two factor XI mutations in a Chinese family with factor XI deficiency

Abstract

We describe a Chinese family with factor XI deficiency, the first reported to date. The proband had factor XI activity of 1% and was heterozygous for two nonsense mutations, an exon-8 C713 fi T mutation resulting in Gln263 fi Term, and an exon-10 C979 fi A mutation resulting in Tyr351 fi Term. Two daughters were heterozygous for the Gln263 fi Term mutation and two for the Try351 fi Term mutation. All showed a reduction of factor XI activity to about 50%. The Gln263 fi Term mutation has been described in two Japanese families, and it remains to be determined whether a common founder exists between the three kindreds. The Try351 fi Term mutation is novel. Am.

Population‐specific spectrum of the F11 mutations in Koreans: evidence for a founder effect

“…The Q263X mutation has been reported repeatedly in Japanse and Chinese patients (9,10,12,13). Structurally, the Q263X mutation codes for a stop 1 TGC9ATATGG 13 3 2 TGC9GCATGG 1 0 3 TGC10GCATGG 1 0 4 TTC9ATATGG 2 0 5 a TTC9ACATGG 9 7 6 TTC9ACATTT 1 0 7 TTA9ACATGG 1 1 8 TTA10GCATGG 2 1 9 TTA11GCATGG 1 1 10 TTA11GCGCGG 4 0 11 CTC9ACATGG 4 0 12 CTA9ACATGG 3 0 13 CTA9GCATTT 2 0 14 CTA10ACATGG 1 0 15 CTA10GCATGG 2 1 16 b CTA10GCATTT 1 8 17 TTA11GCGTGG 0 1 18 TGC9ATATTT 0 1 19 TGC10ATACGG 0 codon after a sequence coding for the third apple domain of the FXI protein, causing truncation of the fourth apple domain which is important for dimerization and secretion of FXI and the serine protease domain (10).…”

“…The Q263X mutation has been reported repeatedly in Japanse and Chinese patients (9, 10, 12, 13). Structurally, the Q263X mutation codes for a stop codon after a sequence coding for the third apple domain of the FXI protein, causing truncation of the fourth apple domain which is important for dimerization and secretion of FXI and the serine protease domain (10).…”

A case of factor XI deficiency caused by compound heterozygous F11 gene mutation

“…C38R mutation has also been found in many French Basque kindreds. The Q263Term was first reported in a Japanese family [5], and so far, it has only been reported in two Japanese families [3,5] and one Chinese family [4]. Our case is the fourth FXI deficiency associated with Q263Term mutation.…”

“…The Q263Term mutation would lead to the synthesis of an unstable truncated FXI protein, lacking part of the heavy chain and the whole light chain. The truncated protein may be degraded intracellularly without secretion [3–5]. This mutation can be traced back to the paternal family.…”

Coagulation factor XI gene analysis in three factor XI deficient Austrian patients

“…The majority of cases reported are of Ashkenazi Jewish origin, where type II (Glu117X) and type III (Phe283Leu) mutations account for more than 95% of cases (5, 6). However, the number of mutations found in other ethnic groups is rapidly increasing (4, 7–29). In Austrian patients only one mutation associated with congenital factor XI deficiency has been reported (30).…”