Cummings C J, Zoghbi H Y
Program in Cell and Molecular Biology, Department of Pediatrics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
Annu Rev Genomics Hum Genet. 2000;1:281-328. doi: 10.1146/annurev.genom.1.1.281.
Within the closing decade of the twentieth century, 14 neurological disorders were shown to result from the expansion of unstable trinucleotide repeats, establishing this once unique mutational mechanism as the basis of an expanding class of diseases. Trinucleotide repeat diseases can be categorized into two subclasses based on the location of the trinucleotide repeats: diseases involving noncoding repeats (untranslated sequences) and diseases involving repeats within coding sequences (exonic). The large body of knowledge accumulating in this fast moving field has provided exciting clues and inspired many unresolved questions about the pathogenesis of diseases caused by expanded trinucleotide repeats. This review summarizes the current understanding of the molecular pathology of each of these diseases, starting with a clinical picture followed by a focused description of the disease genes, the proteins involved, and the studies that have lent insight into their pathophysiology.
在二十世纪的最后十年里，有14种神经系统疾病被证明是由不稳定的三核苷酸重复序列扩增所致，这一曾经独特的突变机制成为了一类不断扩大的疾病的发病基础。根据三核苷酸重复序列的位置，三核苷酸重复疾病可分为两个亚类：涉及非编码重复序列（非翻译序列）的疾病和涉及编码序列（外显子）内重复序列的疾病。在这个快速发展的领域中积累的大量知识提供了令人兴奋的线索，并引发了许多关于由扩增的三核苷酸重复序列引起的疾病发病机制的未解决问题。本综述总结了目前对这些疾病中每一种疾病分子病理学的理解，首先介绍临床症状，然后重点描述疾病基因、相关蛋白质以及有助于深入了解其病理生理学的研究。
