Molecular diagnosis of hemophilia A in Chinese patients by an analysis of inversions in the factor VIII gene.
Hemophilia A is an X-linked bleeding disorder caused by deleterious mutations in the factor VIII gene. An inversion caused by introchromosomal homologous recombination between the A gene located in intron 22 of the factor VIII gene and one of the two telomeric A genes has been recently described as the common cause of about 50% of cases of severe hemophilia A. The rearrangement can be readily detected by a Southern blotting procedure. We report use of this procedure to detect rearrangements in 106 unrelated Chinese hemophilia A cases. In 49.3% of the patients with severe disease an inversion was found, but no inversion was detected in any of the patients with moderate or mild disease. The majority of inversions (91.4%) involved the most distal A gene; in a minority (8.6%) the more proximal A gene was involved. These results indicate that intron 22 inversion is the most important molecular defect causing Chinese hemophilia A and that analysis for intron 22 inversion may be the first-line test in the molecular diagnosis of severe hemophilia A.
Chen
Y D
YD
Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, People's Republic of China.
Zhang
Y Z
YZ
Wu
J S
JS
Wang
H L
HL
Shao
H Z
HZ
Ren
Z R
ZR
Chen
Z
Z
Wang
Z Y
ZY
Zeng
Y T
YT
D044466:Asian People / Q000235:genetics*; D015139:Blotting, Southern; D002681:China; D007446:Chromosome Inversion; D005169:Factor VIII / Q000235:genetics*; D015321:Gene Rearrangement; D005820:Genetic Testing / Q000379:methods*; D006467:Hemophilia A / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male
D005169:Factor VIII