Bakker E, Van Broeckhoven C, Bonten E J, van de Vooren M J, Veenema H, Van Hul W, Van Ommen G J, Vandenberghe A, Pearson P L
Department of Human Genetics, State University of Leiden, The Netherlands.
Nature. 1987;329(6139):554-6. doi: 10.1038/329554a0.
Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease with an incidence of approximately 1 in 3,500 newborn boys. The DMD locus has a high mutation frequency: one third of the cases is thought to result from a new mutation. Linkage studies using probes to detect restriction fragment length polymorphisms and DNA deletion studies have greatly improved DMD carrier detection and prenatal diagnosis. Here we report on two families in which a pERT87 (DXS164) deletion was transmitted to more than one offspring by women who showed no evidence for the mutation in their own somatic (white blood) cells. We also show that the deletion in both siblings in one of the families is identical, indicating that the deletion must have occurred during mitosis in early germline proliferation, leading to a germline mosaicism. This phenomenon may turn out to be a major factor contributing to the induction of DMD mutations, and has important implications for the counselling of DMD families.
杜兴氏肌营养不良症（DMD）是一种严重的X连锁神经肌肉疾病，在新生男婴中的发病率约为1/3500。DMD基因座具有很高的突变频率：据认为，三分之一的病例是由新突变引起的。使用探针检测限制性片段长度多态性的连锁研究和DNA缺失研究极大地改善了DMD携带者检测和产前诊断。在此，我们报告两个家系，其中pERT87（DXS164）缺失由女性传递给多个后代，而这些女性自身的体细胞（白细胞）中未显示出该突变的证据。我们还表明，其中一个家系中两个兄弟姐妹的缺失是相同的，这表明该缺失一定发生在早期种系增殖过程中的有丝分裂期间，导致了种系嵌合体。这种现象可能是导致DMD突变的一个主要因素，并且对DMD家系的遗传咨询具有重要意义。
