Chen Y D, Zhang Y Z, Wu J S, Wang H L, Shao H Z, Ren Z R, Chen Z, Wang Z Y, Zeng Y T
Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, People's Republic of China.
Hematopathol Mol Hematol. 1996;10(1-2):63-7.
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.
甲型血友病是一种X连锁出血性疾病，由凝血因子VIII基因的有害突变引起。最近有研究表明，位于凝血因子VIII基因内含子22中的A基因与两个端粒A基因之一之间发生的染色体内同源重组所导致的倒位，是约50%的重度甲型血友病病例的常见病因。这种重排可通过Southern印迹法轻易检测到。我们报告了使用该方法检测106例非亲属中国甲型血友病患者的重排情况。在49.3%的重症患者中发现了倒位，但在任何中度或轻度疾病患者中均未检测到倒位。大多数倒位（91.4%）涉及最远端的A基因；少数（8.6%）涉及更近端的A基因。这些结果表明，内含子22倒位是导致中国甲型血友病的最重要分子缺陷，并且内含子22倒位分析可能是重度甲型血友病分子诊断的一线检测方法。
