DNA diagnosis of congenital myotonic dystrophy

我们使用DM基因特异性探针（p5B1.4）进行Southern杂交，分析了55例肌强直性营养不良（DM）患者的CTG重复扩增，其中包括25例先天性DM。CTG重复序列在糖尿病患者中从父母传播到儿童严重程度时扩增。糖尿病家族在连续几代中表现出遗传预期、疾病严重程度的增加和发病年龄的提前。先天性糖尿病的传播被认为完全是母系的。在分子分析的基础上，我们报告了首例遗传自无症状父亲的先天性糖尿病患者。基于对先天性糖尿病患者不同组织中CTG重复序列的分析，揭示了躯体不稳定的存在。我们分析了先天性糖尿病患者骨骼肌和淋巴细胞中提取的dna的CTG重复序列的大小。所有患者骨骼肌的大小均比淋巴细胞大1.5 ~ 3.5kb。我们利用合成的DM-PK肽抗原抗体，通过免疫细胞化学方法在活检肌肉和培养肌肉中表达DM-PK。DM-PK在肌肉组织的神经肌肉连接处、肌梭和肌膜中可见。在培养肌肉中，DM-PK在成肌细胞和肌管的胞浆中表达。

We have analyzed CTG repeat expansion in 55 myotonic dystrophy (DM) patients, including 25 congenital DM by Southern hybridization using DM gene specific probe (p5B1.4). The CTG repeat was expanded in DM patients when transmitted from parent to child severity. DM families showed genetic anticipation, an increase in disease severity and earlier age of onset in successive generations. The transmission of congenital DM was considered exclusively maternal. We present the first congenital DM patients transmitted from asymptomatic father on the basis of molecular analysis. Based on analysis of CTG repeat in various tissues from a patient of congenital DM,the presence of somatic instability was disclosed.We have analyzed the size of the CTG repeat of DNAs extracted from skeletal muscle and lymphocytes in congenital DM patients. The size from skeletal muscle showed an increase of about 1.5kb to 3.5kb larger than that from lymphocytes in all patients.We present expression of DM-PK on biopsied muscles and cultured muscles by immunocytochemistry using antibody aganist synthetic DM-PK peptide antigen. DM-PK was observed in neuromuscular junctions, muscle spindle, and sarcolemma on biopsied muscles. On cultured muscles, DM-PK was expressed in cytoplasma of myoblast and myotube.