Thromb Haemost 2002; 87(02): 273-276
DOI: 10.1055/s-0037-1612984
Letters to the Editor
Schattauer GmbH

Non-Inversion Factor VIII Mutations in 80 Hemophilia A Families Including 24 with Alloimmune Responses

Miao-Liang Liu
1   Puget Sound Blood Center and the Department of Medicine, University of Washington, Seattle, Washington, USA
,
Shelley Nakaya
1   Puget Sound Blood Center and the Department of Medicine, University of Washington, Seattle, Washington, USA
,
Arthur R. Thompson
1   Puget Sound Blood Center and the Department of Medicine, University of Washington, Seattle, Washington, USA
› Institutsangaben
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Publikationsverlauf

Received 09. Juli 2001

Accepted after resubmission 14. November 2001

Publikationsdatum:
13. Dezember 2017 (online)

Summary

Heteroduplex screening identified 74 small mutations in the factor VIII genes of 72 families with hemophilia A. In addition, patients from 3 families with high titer inhibitors had partial gene deletions and 5 unrelated families that were negative for heteroduplex formation had a mutation on direct sequencing. The latter had mild hemophilia A with an inhibitor, and sequencing their exon 23 fragments found a transition predicting a recurrent Arg2150 to His. Of 69 distinct mutations (including the 3 partial gene deletions), 47 are novel. Of small mutations, 51 were missense (one possibly a normal variant and two that could also alter splicing) at 39 sites, 13 were small deletions or insertions (3 inframe and one a normal variant in an intron), 13 were nonsense at 12 sites and 2 altered intron splice junctions. In 24 families, at least one affected member had evidence for an alloimmune response to factor VIII; of these, 11 were associated with missense mutations. In 14 families, de novo origin was demonstrated.

 
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