Timchenko L, Monckton D G, Caskey C T
Department of Molecular and Human Genetics, Baylor College of Medicine, Texas Medical Center, Houston 77030, USA.
Semin Cell Biol. 1995 Feb;6(1):13-9. doi: 10.1016/1043-4682(95)90010-1.
Myotonic dystrophy (DM) is caused by the amplification of CTG repeats in the 3' untranslated region of a gene encoding a protein homologous to serine/threonine protein kinases. In DM patients the CTG repeats are extremely unstable, varying in length from patient to patient and generally increasing in length in successive generations. There is a strong correlation between the size of the repeats and the age of onset and severity of the disease. The molecular basis of the effect of the CTG expansion on the development of the DM phenotype continues to be investigated. The first working hypothesis of the molecular mechanism of DM was a reduction in steady-state myotonin-protein kinase (Mt-PK) mRNA and protein levels. However, although the consensus finding is that the Mt PK mRNA and protein levels are decreased in DM patients, it is still not clear if this reduction leads directly to the DM phenotype. In this short review we discuss the molecular aspects of CTG instability and the expression of the myotonin-protein kinase gene in normal and DM populations.
强直性肌营养不良（DM）是由编码一种与丝氨酸/苏氨酸蛋白激酶同源的蛋白质的基因3'非翻译区中CTG重复序列的扩增引起的。在DM患者中，CTG重复序列极其不稳定，其长度在不同患者之间存在差异，并且在连续几代中通常会变长。重复序列的大小与疾病的发病年龄和严重程度之间存在很强的相关性。CTG扩增对DM表型发展的影响的分子基础仍在研究中。DM分子机制的第一个工作假说是稳态肌强直性蛋白激酶（Mt-PK）mRNA和蛋白质水平降低。然而，尽管一致的发现是DM患者中Mt PK mRNA和蛋白质水平降低，但仍不清楚这种降低是否直接导致DM表型。在这篇简短的综述中，我们讨论了CTG不稳定性的分子方面以及正常人群和DM人群中肌强直性蛋白激酶基因的表达。
