Characterization of five partial deletions of the factor VIII gene

H. Youssoufian, S. E. Antonarakis, S. Aronis, G. Tsiftis, D. G. Phillips, H. H. Kazazian

Research output: Contribution to journalArticle

Abstract

Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, we have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2,5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes.

Original languageEnglish (US)
Pages (from-to)3772-3776
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number11
DOIs
StatePublished - Aug 14 1987
Externally publishedYes

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