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

• Published in: The Journal of clinical investigation Vol. 90; no. 2; pp. 315 - 319
• Main Authors: Kamura, T, Okamura, T, Murakawa, M, Tsuda, H, Teshima, T, Shibuya, T, Harada, M, Niho, Y
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.08.1992
• Subjects: Alleles; Base Sequence; Biological and medical sciences; cDNA; coagulation factor XIII; deficiency; deletion; exons; Factor XIII - genetics; Factor XIII Deficiency - genetics; Gene Expression; Genes; Hematologic and hematopoietic diseases; Humans; Male; man; Medical sciences; Middle Aged; Molecular Sequence Data; Mutation; nucleotide sequence; Oligodeoxyribonucleotides - chemistry; Pedigree; Polymerase Chain Reaction; RNA, Messenger - genetics; Human; Molecular form; Nucleotide sequence; Deficiency; Factor XIII; Hemopathy; Case study; Exon; Gene; Deletion; Molecular biology; Coagulation factor; Coagulopathy
• ISSN: 0021-9738
• DOI: 10.1172/JCI115864

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.