Molecular cytogenetic study of the myotonic dystrophy by in situ hybrdization (ISH)

强直性肌营养不良（Myotonic dystrophy，DM）是一种常染色体显性遗传病，其致病基因编码DM蛋白激酶（DMPK），位于染色体19q13。本研究采用原位杂交技术（ISH）对DM的分子发病机制进行了初步探讨，结果表明：（1）来自突变等位基因的DMPK转录本在患者LCL细胞核中积累，（2）积累的转录物主要是来自突变等位基因的mRNA而不是前体mRNA。此外，通过分子生物学研究发现，患者细胞核中的mRNA量显著高于正常个体细胞核中的mRNA量，突变型等位基因转录的加工mRNA在患者细胞核中积累的结果可能为研究各种临床疾病患者的发病机制提供了一个关键点。特点，我们将进一步研究解决问题。

Myotonic dystrophy (DM) is an autosomal dominant disease, whose responsible gene encodes DM protein kinase (DMPK) and is located on the chromosome 19q 13. Though DM is caused by abnormal expansion of triplet (CTG) repeat at 3'UTR of DMPK gene, the molecular mechanism of the causing disease have been still unknown.In this study, we have gained the following results by using in situ hybridization (ISH) method to search the molecular pathogenesis of DM.It shows that (1) DMPK transcripts from mutant allele were accumulated in the nuclei of the LCL obtained from the patients, (2) the accumulated transcripts were mainly mRNA rather than pre-mRNA from mutant allele. Moreover, the amount of mRNA in the nuclei of the patients was found to be significantly higher than those in the nuclei of the normal individuals by the molecular biological study, which supports the result by ISH method described above.As the result that the processed mIRNA transcribed from mutant allele are accumulated in the nuclei of the patients may provide a key point to study the pathogenesis of the patients with various clinical features, we will make a further study to resolve the problem.