Brunner H G, Spaans F, Smeets H J, Coerwinkel-Driessen M, Hulsebos T, Wieringa B, Ropers H H
Department of Human Genetics, Radboud Hospital, Nijmegen, The Netherlands.
Neurology. 1991 Jan;41(1):80-4. doi: 10.1212/wnl.41.1.80.
We identified a large kindred that shows classical myotonic dystrophy (MyD), together with hereditary motor and sensory neuropathy (HMSN) in some individuals, and HMSN alone in others. A previous study of this family has shown cosegregation of the MyD and HMSN phenotypes with the Lutheran and secretor loci in some branches of the family, indicating linkage to chromosome 19. We reanalyzed this family with 2 recombinant DNA marker systems from the ApoC2 locus on chromosome 19. Our results demonstrate that all affected individuals have inherited a unique ApoC2 haplotype that was not found in their clinically and electrophysiologically normal sibs. We also obtained evidence against involvement of the HMSN I locus on chromosome 17. In this family, a moderately severe neuropathy may be the only clinical sign of MyD for many years. Our results are consistent with an unusual neuropathic mutation at the MyD gene. However, involvement of 2 closely linked genes (1 for MyD and the other for HMSN) can also explain our findings.
我们鉴定出一个大家族，其中一些个体表现为典型的强直性肌营养不良（MyD）以及遗传性运动和感觉神经病（HMSN），另一些个体仅表现为HMSN。此前对这个家族的一项研究表明，在家族的一些分支中，MyD和HMSN表型与路德血型和分泌型基因座共分离，提示与19号染色体连锁。我们用来自19号染色体载脂蛋白C2（ApoC2）基因座的2个重组DNA标记系统对这个家族进行了重新分析。我们的结果表明，所有患病个体都继承了一种独特的ApoC2单倍型，而在其临床和电生理正常的同胞中未发现这种单倍型。我们还获得了证据，排除了17号染色体上HMSN I基因座的参与。在这个家族中，中度严重的神经病可能多年来一直是MyD的唯一临床体征。我们的结果与MyD基因存在异常的神经病性突变一致。然而，2个紧密连锁的基因（1个与MyD有关，另一个与HMSN有关）的参与也可以解释我们的发现。
