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BRIEF REPORT
From the Department of Human Genetics, University of
Würzburg, Biozentrum, Würzburg, Germany; the Department of
Experimental Haematology and Transfusion Medicine and the Department of
Clinical Biochemistry, University of Bonn, Bonn, Germany; and the Max
Planck Institut für Molekulare Genetik, Berlin, Germany.
The intron 22 inversion represents the most prevalent
factor VIII gene defect in severe hemophilia A, accounting
for about 40% of all mutations. It is hypothesized that the inversion
mutations occur almost exclusively in germ cells during meiotic cell
division by intrachromosomal recombination between 1 of 2 telomeric
copies of the Int22h region and its intragenic homologue. The
majority of inversion mutations originate in male germ cells, where the lack of bivalent formation may facilitate flipping of the telomeric end
of the single X chromosome. This is the first intron 22 inversion that presents as a somatic mosaicism in a female, affecting
only about 50% of lymphocyte and fibroblast cells of the proposita. Supposing a post-zygotic de novo mutation as the usual cause of somatic mosaicism, the finding would imply that the intron 22 inversion
mutation is not restricted to meiotic cell divisions but can also occur
during mitotic cell divisions, either in germ cell precursors or in
somatic cells. This article has been cited by other articles:
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| Copyright © 2000 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
