Nonsense and missense mutations in hemophilia A: Estimate of the relative mutation rate at CG dinucleotides

H. Youssoufian, S. E. Antonarakis, W. Bell, A. M. Griffin, Haig Kazazian

Research output: Contribution to journalArticle

Abstract

Hemophilia A is an X-linked disease of coagulation caused by deficiency of factor XIII. Using cloned cDNA and synthetic oligonucleotide probes, we have now screened 240 patients and found CG-to-TG transitions in an exon in nine. We have previously reported four of these patients; and here we report the remaining five, all of whom were severely affected. In one patient a TaqI site was lost in exon 23, and in the other four it was lost in exon 24. The novel exon 23 mutation is a CG-to-TG substitution at the codon for amino acid residue 2166, producing a nonsense codon in place of the normal codon for arginine. Similarly, the exon 24 mutations are also generated by CG-to-TG transitions, either on the sense strand producing nonsense mutations or on the antisense strand producing missense mutations (Arg to Gln) at position 2228. The novel missense mutations are the first such mutations observed in association with severe hemophilia A. These results provide further evidence that recurrent mutations are not uncommon in hemophilia A, and they also allow us to estimate that the extent of hypermutability of CG dinucleotides is 10-20 times greater than the average mutation rate for hemophilia A.

Original languageEnglish (US)
Pages (from-to)718-725
Number of pages8
JournalAmerican Journal of Human Genetics
Volume42
Issue number5
StatePublished - 1988

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Nonsense Codon
Hemophilia A
Mutation Rate
Missense Mutation
Exons
Mutation
Codon
Factor XIII Deficiency
Oligonucleotide Probes
Arginine
Complementary DNA
cytidylyl-3'-5'-guanosine
Amino Acids

ASJC Scopus subject areas

  • Genetics

Cite this

Nonsense and missense mutations in hemophilia A : Estimate of the relative mutation rate at CG dinucleotides. / Youssoufian, H.; Antonarakis, S. E.; Bell, W.; Griffin, A. M.; Kazazian, Haig.

In: American Journal of Human Genetics, Vol. 42, No. 5, 1988, p. 718-725.

Research output: Contribution to journalArticle

Youssoufian, H. ; Antonarakis, S. E. ; Bell, W. ; Griffin, A. M. ; Kazazian, Haig. / Nonsense and missense mutations in hemophilia A : Estimate of the relative mutation rate at CG dinucleotides. In: American Journal of Human Genetics. 1988 ; Vol. 42, No. 5. pp. 718-725.
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