Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Eur J Hum Genet. 2012 Dec;20(12):1203-8. doi: 10.1038/ejhg.2012.108. Epub 2012 May 30.
Myotonic dystrophy is an autosomal dominant, multisystem disorder that is characterized by myotonic myopathy. The symptoms and severity of myotonic dystrophy type l (DM1) ranges from severe and congenital forms, which frequently result in death because of respiratory deficiency, through to late-onset baldness and cataract. In adult patients, cardiac conduction abnormalities may occur and cause a shorter life span. In subsequent generations, the symptoms in DM1 may present at an earlier age and have a more severe course (anticipation). In myotonic dystrophy type 2 (DM2), no anticipation is described, but cardiac conduction abnormalities as in DM1 are observed and patients with DM2 additionally have muscle pain and stiffness. Both DM1 and DM2 are caused by unstable DNA repeats in untranslated regions of different genes: A (CTG)n repeat in the 3'-UTR of the DMPK gene and a (CCTG)n repeat in intron 1 of the CNBP (formerly ZNF9) gene, respectively. The length of the (CTG)n repeat expansion in DM1 correlates with disease severity and age of onset. Nevertheless, these repeat sizes have limited predictive values on individual bases. Because of the disease characteristics in DM1 and DM2, appropriate molecular testing and reporting is very important for the optimal counseling in myotonic dystrophy. Here, we describe best practice guidelines for clinical molecular genetic analysis and reporting in DM1 and DM2, including presymptomatic and prenatal testing.
强直性肌营养不良症是一种常染色体显性、多系统疾病，其特征为肌强直性肌病。1 型强直性肌营养不良症（DM1）的症状和严重程度范围广泛，从严重和先天性形式，这些形式经常由于呼吸缺陷而导致死亡，到迟发性秃发和白内障。在成年患者中，可能会出现心脏传导异常，导致寿命缩短。在随后的几代中，DM1 的症状可能会更早出现，并且病程更严重（预期）。在 2 型强直性肌营养不良症（DM2）中，没有描述预期，但会观察到与 DM1 相同的心脏传导异常，并且 DM2 患者还会出现肌肉疼痛和僵硬。DM1 和 DM2 均由不同基因的非翻译区中不稳定的 DNA 重复引起：DMPK 基因 3'UTR 中的 A（CTG）n 重复和 CNBP（以前为 ZNF9）基因内含子 1 中的（CCTG）n 重复。DM1 中（CTG）n 重复扩展的长度与疾病严重程度和发病年龄相关。尽管如此，这些重复大小在个体基础上的预测价值有限。由于 DM1 和 DM2 的疾病特征，在强直性肌营养不良症中进行适当的分子检测和报告对于最佳咨询非常重要。在这里，我们描述了 DM1 和 DM2 临床分子遗传学分析和报告的最佳实践指南，包括症状前和产前检测。
