Molecular genetic analysis of factor XI deficiency: Identification of fivenovel gene alterations and the origin of type II mutation in Portuguese families
C. Ventura et al., Molecular genetic analysis of factor XI deficiency: Identification of fivenovel gene alterations and the origin of type II mutation in Portuguese families, THROMB HAEM, 84(5), 2000, pp. 833-840
Coagulation Factor XI (FXI) deficiency is an inherited autosomal recessive
mild bleeding disorder. In this study, we report the molecular genetic anal
ysis of FXI deficiency in six unrelated families of Portuguese origin. The
Jewish type II mutation was found in two families, of seemingly Portuguese
origin. Haplotype analysis in these families demonstrated that this mutatio
n is of Jewish origin. In the remaining families, five novel FXI mutations
have been identified. Two of these mutations (FXI IVS K -10T-->A and FXI 10
26G-->T, cd 324) affect the FXI pre-mRNA splicing. A further two (FXI 307 i
ns AAGCAAT, ed 85 and FXI 1072 del A, ed 340) introduce frameshifts leading
to premature termination codons. The FXI splicing mutation, 1026G-->T ed 3
24, was found in compound heterozygosity with missense mutation FXI K518N.
Analysis of the FXI mRNA from the latter genotype demonstrated new donor sp
lice site usage. All reported mutations most likely result in functional nu
ll-alleles. In addition, three novel polymorphisms have been identified: at
nt -138 in intron A, at codon D125 in exon 5 and at codon T249 in exon 8.