Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A

Delia Lakich, Haig H. Kazazian, Stylianos E. Antonarakis, Jane Gitschier

Research output: Contribution to journalArticle

Abstract

Mutations in the factor VIII gene have been discovered for barely more than half of the examined cases of severe haemophilia A. To account for the unidentified mutations, we propose a model based on the possibility of recombination between homologous sequences located in intron 22 and upstream of the factor VIII gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. We present evidence to support this model and describe a Southern blot assay that detects the inversion. These findings should be valuable for genetic prediction of haemophilia A in ˜ 45% of families with severe disease.

Original languageEnglish (US)
Pages (from-to)236-241
Number of pages6
JournalNature genetics
Volume5
Issue number3
DOIs
StatePublished - Nov 1993

ASJC Scopus subject areas

  • Genetics

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