Characterization of a novel large deletion caused by double-stranded breaks in 6-bp microhomologous sequences of intron 11 and 12 of the F13A1 gene

Coagulation Factor XIII is a heterotetrameric protransglutaminase which stabilizes preformed fibrin clots by covalent crosslinking them. Inherited homozygous or compound heterozygous deficiency of coagulation Factor XIII (FXIII) is a rare severe bleeding disorder affecting 1 in 2 million individuals. Most of the patients with inherited FXIII deficiency described in the literature carry F13A1 gene point mutations (missense, nonsense and splice site defects), whereas large deletions (>0.5 kb in size) are underrepresented. In this article we report for the first time the complete characterization of a novel homozygous F13A1 large deletion covering the entire exon 12 in a young patient with a severe FXIII-deficient phenotype from France. Using primer walking on genomic DNA we have identified the deletion breakpoints in the region between g.6.143,016–g.6.148,901 caused by small 6-bp microhomologies at the 5´ and 3´ breakpoints. Parents of the patient were heterozygous carriers. Identification of this large deletion offers the possibility of prenatal diagnosis for the mother in this family who is heterozygous for this deletion.