Meiner A, Wolf C, Carey N, Okitsu A, Johnson K, Shelbourne P, Kunath B, Sauermann W, Thiele H, Kupferling P
Institute of Human Genetics, University of Leipzig, Germany.
J Med Genet. 1995 Aug;32(8):645-9. doi: 10.1136/jmg.32.8.645.
Myotonic dystrophy (DM) is associated with the expansion and instability of a trinucleotide (CTG) repeat at the DM locus on chromosome 19. Direct genomic analysis in the German population was carried out on 18 DM families, six families with equivocal diagnosis, 69 subjects with equivocal clinical diagnosis, and 100 controls using the polymerase chain reaction (PCR) and a refined Southern protocol. In the majority of the cases molecular analysis confirmed the clinical diagnosis. These included seven cases of congenital DM (CDM) with widely differing gene expansions and instabilities. In most DM families the expanded fragment became larger in successive generations, but we also identified four families with contractions and two families that showed stability of the enlarged fragment during transmission. In four clinically defined DM patients we were unable to detect enlarged CTG repeats. Sequencing of each exon of the DM gene in two of these patients failed to show any mutations. Our cases have important implications for genetic counselling of DM families, highlighting both the diagnostic value of direct genomic analysis and its limitations.
强直性肌营养不良（DM）与19号染色体上DM位点的三核苷酸（CTG）重复序列的扩增和不稳定性有关。我们对德国人群进行了直接基因组分析，研究对象包括18个DM家族、6个诊断不明确的家族、69例临床诊断不明确的受试者以及100名对照，采用聚合酶链反应（PCR）和改良的Southern杂交方法。在大多数病例中，分子分析证实了临床诊断。其中包括7例先天性DM（CDM），其基因扩增和不稳定性差异很大。在大多数DM家族中，扩增片段在连续几代中变得更大，但我们也发现了4个收缩的家族和2个在传递过程中扩增片段显示稳定的家族。在4例临床诊断为DM的患者中，我们未能检测到CTG重复序列扩增。对其中2例患者的DM基因各外显子进行测序，未发现任何突变。我们的病例对DM家族的遗传咨询具有重要意义，既突出了直接基因组分析的诊断价值，也显示了其局限性。
