A novel DNA inversion causing severe hemophilia A
JA Naylor, P Nicholson, Anne Goodeve, S Hassock, I Peake and F Giannelli
Division of Medical and Molecular Genetics, United Medical and Dental
Schools of Guy's and St. Thomas's Hospitals, London, UK.
Almost half of all cases of severe hemophilia A are caused by recurrent DNA
inversions, which disrupt the factor VIII (FVIII) gene. These inversions
generally occur between a region of intron 22 (int22h) and one of two
homologous copies of this region, located 300 to 400 kb telomeric to the
FVIII gene. They are routinely detected by a Bcl I Southern blot assay in
which the sizes of two of the three normal hybridization bands are
characteristically altered. However, atypical hybridization patterns have
been observed, and this report describes the first detailed analysis of a
hemophilia A patient with such a pattern. The abnormal result was found to
be caused by a novel FVIII inversion involving an extra copy of int22h from
a site only 70 to 200 kb telomeric of the FVIII gene. Polymerase chain
reaction (PCR) allowed one of the inversion junctions to be analyzed,
showing that the int22h sequence at this inversion junction was truncated.
This patient and his novel inversion provide further evidence that int22h
is associated with instability in Xq28.
Volume 87,
Issue 8,
pp. 3255-3261,
04/15/1996
Copyright © 1996 by The American Society of Hematology
