A 20.7 kb Deletion within the Factor VIII Gene Associated with LINE-1 Element Insertion

Neil Van de Water; Ruth Williams; Paul Ockelford; Peter Browett

doi:10.1055/s-0037-1615098

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(05): 938-942
DOI: 10.1055/s-0037-1615098

Review Article

Schattauer GmbH

A 20.7 kb Deletion within the Factor VIII Gene Associated with LINE-1 Element Insertion

Neil Van de Water

¹From the Department of Haematology, Auckland Hospital and Department of Molecular Medicine, University of Auckland, Auckland, New Zealand

,

Ruth Williams

¹From the Department of Haematology, Auckland Hospital and Department of Molecular Medicine, University of Auckland, Auckland, New Zealand

,

Paul Ockelford

¹From the Department of Haematology, Auckland Hospital and Department of Molecular Medicine, University of Auckland, Auckland, New Zealand

,

Peter Browett

¹From the Department of Haematology, Auckland Hospital and Department of Molecular Medicine, University of Auckland, Auckland, New Zealand

› Author Affiliations

Abstract

Summary

Large deletions within the factor VIII gene account for approximately 5% of the mutations causing haemophilia A. The characterization of such mutations can provide insights into the molecular mechanisms of these and other deletions in man. We have analyzed a 20.7 kb deletion spanning exons 15 to 20 within the factor VIII gene in a patient with severe haemophilia A. Long range PCR was used to investigate the extent of the deletion and to provide a template for sequencing across the deletion breakpoint. A 38-base insertion homologous to the 3’ region of a LINE-1 (L1) element was detected at the breakpoint of the deletion. Normal sequence at the 5’ breakpoint in intron 14 was homologous to an L1 flanking region and normal sequence at the 3’ breakpoint in intron 20 was homologous to an adjacent sequence within the same L1 flanking region. A molecular mechanism for the deletion involving retrotransposition of a readthrough product of an L1 element plus its 3’ flanking region is suggested.

Full Text

References

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