title: 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.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kamura
authors.forename: T
authors.initials: T
authors.lastname: Okamura
authors.forename: M
authors.initials: M
authors.lastname: Murakawa
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.forename: T
authors.initials: T
authors.lastname: Teshima
authors.forename: T
authors.initials: T
authors.lastname: Shibuya
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: Y
authors.initials: Y
authors.lastname: Niho
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005176:Factor XIII / Q000235:genetics; D005177:Factor XIII Deficiency / Q000235:genetics*; D015870:Gene Expression; D005796:Genes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D005176:Factor XIII