title: 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.
abstract: 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.
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn , Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn , Bonn, Germany.
authors.forename: Vytautas
authors.initials: V
authors.lastname: Ivaškevičius
authors.affiliation: Institut d'Hématologie, Hŏpital Cardiologique , Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Zawadzki
authors.affiliation: Institut d'Hématologie, Hŏpital Cardiologique , Lille, France.
authors.forename: Jenny
authors.initials: J
authors.lastname: Goudemand
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn , Bonn, Germany.
authors.forename: Arijit
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn , Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg