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Thromb Haemost 1998; 79(03): 479-485
DOI: 10.1055/s-0037-1614929
Review Articles
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Novel Deletion and Insertion Mutations Cause Splicing Defects, Leading to Severe Reduction in mRNA Levels of the A Subunit in Severe Factor XIII Deficiency

Tomonori Izumi
1   Department of Molecular Patho-Biochemistry, Yamagata University School of Medicine, Yamagata, Japan
,
Utako Nagaoka
1   Department of Molecular Patho-Biochemistry, Yamagata University School of Medicine, Yamagata, Japan
,
Tetsuo Saito
1   Department of Molecular Patho-Biochemistry, Yamagata University School of Medicine, Yamagata, Japan
,
Junki Takamatsu
1   Department of Medicine I, Nagoya University School of Medicine, Nagoya, Japan
,
Hidehiko Saito
1   Department of Medicine I, Nagoya University School of Medicine, Nagoya, Japan
,
Akitada Ichinose
1   Department of Molecular Patho-Biochemistry, Yamagata University School of Medicine, Yamagata, Japan
› Author Affiliations
Further Information

Publication History

Received 05 May 1997

Accepted 16 October 1997

Publication Date:
07 December 2017 (online)

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Summary

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 defective 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.

 

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