Deficiency of coagulation factor XIII A subunit caused by the dinucleotide deletion at the 5' end of exon III.

Abstract

A congenital deficiency of the coagulation Factor XIII A subunit (F XIII A) is a rare autosomal recessive disorder that is characterized by a life-long bleeding tendency complicated by a difficulty in healing. Thus far, no molecular genetic analysis of this disorder has been reported. In this study, we demonstrate the molecular abnormalities in a family with this disorder. We performed Northern blot analysis of peripheral blood monocytes obtained from the propositus and found a 4-kb single band of F XIII A mRNA whose size was identical with that of normal subjects. Exons II-XV, which encode all the amino acids, were individually amplified by a polymerase chain reaction (PCR). All PCR products from the propositus had lengths indistinguishable from those of the wild type on agarose gel, suggesting that this defect results from either a point mutation or a short deletion/insertion. The sequencing of F XIII A cDNA from the propositus revealed a deletion of the dinucleotide AG within the AGAG repeat at the position of 210 to 213. Concerning the genomic sequence, a deletion of dinucleotide AG was also demonstrated in the intron B-exon III boundary. This deletion appeared to cause a frameshift mutation making a new stop codon shortly thereafter, and leading to a deficiency of plasma F XIII A. The heterozygosity of the F XIII A deficiency in the patient's offspring was documented by the nucleotide sequences of their exon III. (J. Clin. Invest. 1992. 90:315-319.)

Factor Xiii Deficiency

“…A two‐base AG deletion at the intron 2 and exon 3 splice junction also gives rise to an abnormally spliced transcript where the first two nucleotides of exon 3 are skipped ( Table IV; Kamura et al , 1992 ). A 20‐base deletion at the exon 1 and intron 1 splice junction has also been described ( Izumi et al , 1998 ).…”

No Association of Factor XIII Val34Leu Polymorphism with Primary Intracerebral Hemorrhage and Healthy Controls in Korean Population

“…FXIIIB is comprised of 641 amino acids with 10 tandem repeats of 60 amino acids each and its coding region has been assigned to chromosome 1q31-32 (8). Only three mutations have been reported in the gene of FXIIIA (9)(10)(11), and two mutations in the gene of FXIIIB (12). Both genes exhibit common protein polymorphisms among various population groups (13,14).…”

Factor XIII Deficiency

“…Since the first molecular mutation of FXIII deficiency was published in 1992, there have now been over 70 mutations reported [41,42]. The majority of the mutations for FXIII-A are due to missense or nonsense mutations ( The vast majority of FXIII-deficient patients have mutations in the F13A gene, with more than 60 different types of mutations reported.…”