title: Novel deletion and insertion mutations cause splicing defects, leading to severe reduction in mRNA levels of the A subunit in severe factor XIII deficiency.
abstract: In order to explore molecular mechanisms for factor XIII deficiency, a patient (Nagoya I) was examined at the DNA and RNA levels. Nucleotide sequence analysis of the patient's DNA amplified by PCR revealed that he had a 20 bp deletion at the boundary of exon I/intron A, and an insertion of T in the invariant GT dinucleotide at the splicing donor site of exon IV/intron D. The presence of these heterozygous mutations was confirmed by restriction digestion of the amplified fragments of the proband and his parents. RT-PCR analysis demonstrated that only one kind of mRNA without exon IV was detected in Nagoya I, although its level was greatly reduced to less than 5% of normal. The other detective allele of the A subunit gene containing the 20 bp deletion was not detected. Thus, both mutations impaired normal processing of mRNA for the A subunit, resulting in his severe factor XIII deficiency.
authors.affiliation: Department of Molecular Patho-Biochemistry, Yamagata University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Izumi
authors.forename: U
authors.initials: U
authors.lastname: Nagaoka
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: J
authors.initials: J
authors.lastname: Takamatsu
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: A
authors.initials: A
authors.lastname: Ichinose
mesh_terms: D005176:Factor XIII / Q000235:genetics*; D005177:Factor XIII Deficiency / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D011110:Polymorphism, Genetic; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D012333:RNA, Messenger; D005176:Factor XIII