Naylor J A, Green P M, Rizza C R, Giannelli F
Division of Medical & Molecular Genetics, United Medical School, Guy's Hospital, London, UK.
Lancet. 1992 Oct 31;340(8827):1066-7. doi: 10.1016/0140-6736(92)93080-7.
Using an mRNA-based method to examine haemophilia A mutations we provide an explanation for the puzzling report that half of the mutations causing severe disease are not detected by analysis of the putative promoter, exons, and most exon/intron boundaries of the factor VIII gene. An unusual cluster of mutations involving regions of intron 22 not examined earlier leads to defective joining of exons 22 and 23 in the mRNA and caused haemophilia A in 10/24 severely affected UK patients.
我们使用基于mRNA的方法检测甲型血友病突变，对一份令人困惑的报告做出了解释：通过分析凝血因子VIII基因的推定启动子、外显子以及大多数外显子/内含子边界，无法检测到导致严重疾病的一半突变。一个涉及22号内含子先前未检测区域的异常突变簇，导致mRNA中外显子22和23连接缺陷，并在24名受严重影响的英国患者中的10名引发了甲型血友病。
