[Characterization of a large deletion that leads to congenital factor XIII deficiency]

Congenital factor XIII deficiency is a rare bleeding disorder that is inherited in an autosomal recessive manner with a frequency of 1 per 2 million individuals in the human population. In Japan, 53 cases of factor XIII deficiency were registered in the national survey for blood coagulation disorders in 2006. One hundred twenty-three cases were listed in the international Factor XIII Registry (http://www.f13-database.de/) by October 2007. The most frequent genomic abnormalities among the registered cases are point mutations; nucleotide deletions have been identified in only 16 cases. Most deletions are less than 20 bp; only 2 large deletions have been reported. However, detailed studies in either of these 2 cases have not been performed. We analyzed a case of congenital factor XIII deficiency. The patient is Japanese born to consanguineous parents, and his factor XIII A antigen and activity levels are both less than 10% of normal. The LA-PCR product for exons 4-6 of the factor XIII gene was 5 kb smaller than expected. The deletion is exactly 5984 bp long, including the entire exon 5. This finding suggests that the deletion caused a frameshift that produced a premature termination codon in exon 6. Deletions usually occur in repetitive sequences, but repetitive sequences were not found around this deletion. The semiquantified F13A1 mRNA level in the patient sample was only 1% of normal, and suggests that the mRNA surveillance system (nonsense-mediated mRNA decay) may be involved.