Deficiency of factor XIII gene in Chinese: 3 novel mutations

A defect in the factor XIII gene can result in lifelong bleeding tendency. In 3 Chinese families, hereditary coagulation factor XIII deficiency was diagnosed on the basis of the clinical syndrome and solubility of fibrin clot in 5 mol/L urea. We sequenced all of the FXIIIA gene exons and the flanking region and found 3 novel defects in the factor XIII gene. First, C --> G transition at nucleotide (nt) position 1241 in exon 10 results in substitution of Ser413 with Trp. Second, C --> T transition at nt232 in exon 3 results in Arg 77 --> Cys. The third mutation is in exon 5: del-aa at nt598 (codon 191) causes frameshift and premature termination. In the cytoplasm of 3 probands the FXIII gene was normal at the messenger RNA level. Three mutations may affect FXIIIA protein conformation or incorrect protein folding and lead to formation of mutant FXIII that is very unstable and rapidly degraded in cytoplasm.