Variant of intron 22 inversions in the factor VIII gene in severe hemophilia A.
Recurrent DNA inversions, which disrupt the factor VIII (FVIII) gene, 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. This report describes a patient with severe hemophilia A and a high level inhibitor with atypical hybridization patterns. A Bcl I Southern blot assay was altered to 17.5, 16, and 14 kb. His mother and two out of four aunts tested had normal and abnormal restriction patterns which led to a total of five different fragments, suggesting that they were carriers. The Xba I plus Kpn I restriction fragment-length polymorphism in intron 22 by Southern blotting using the same probe (probe a) yielded the 6.2 kb polymorphic band, with a clearly separated 6.6 kb band from the non-factor VIII region; an alternative int22h hybridization probe (probe x) detected no additional fragment. These results suggest that probe a as well as probe x could recognize an intron-22-sized fragment. This report shows a variation in the number of int22h copies although we could not find the inversion junction.
Yamazaki
E
E
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Mohri
H
H
Inaba
H
H
Harano
H
H
Kanamori
H
H
Okubo
T
T
D000328:Adult; D007446:Chromosome Inversion; D005169:Factor VIII / Q000235:genetics*; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D010375:Pedigree
D005169:Factor VIII