Novel deletion and insertion mutations cause splicing defects, leading to severe reduction in mRNA levels of the A subunit in severe factor XIII deficiency.
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.
Izumi
T
T
Department of Molecular Patho-Biochemistry, Yamagata University School of Medicine, Japan.
Nagaoka
U
U
Saito
T
T
Takamatsu
J
J
Saito
H
H
Ichinose
A
A
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
D012333:RNA, Messenger; D005176:Factor XIII