title: A 20.7 kb deletion within the factor VIII gene associated with LINE-1 element insertion.
abstract: 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.
authors.affiliation: Department of Haematology, Auckland Hospital, University of Auckland, New Zealand. n.vandewater@auckland.ac.nz
authors.forename: N
authors.initials: N
authors.lastname: Van de Water
authors.forename: R
authors.initials: R
authors.lastname: Williams
authors.forename: P
authors.initials: P
authors.lastname: Ockelford
authors.forename: P
authors.initials: P
authors.lastname: Browett
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D004251:DNA Transposable Elements / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017384:Sequence Deletion
chemical_list: D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; C077214:L1Hs-encoded protein p40, human; D005169:Factor VIII