Müller U, Graeber M B, Haberhausen G, Köhler A
Institut für Humangenetik, Justus-Liebig-Universität, Giessen, Germany.
J Neurol Sci. 1994 Jul;124(2):119-40. doi: 10.1016/0022-510x(94)90318-2.
Over the past few years, molecular neurogenetics has developed into one of the most promising and active research fields. The new discipline applies modern molecular genetic techniques to the investigation of classical neurological disorders. In the following article, a definition of neurogenetic disease is introduced, the molecular basis of four groups of neurogenetic disorders is described and recent diagnostic developments are presented. The first group of diseases is caused by trinucleotide expansions. "Expanding" trinucleotide repeats were not known to occur in any species until about three years ago. Today, disorders such as Huntington's disease, spinocerebellar ataxia type 1, fragile X mental retardation, spinobulbar muscular atrophy and myotonic dystrophy are all known to be caused by the expansion of trinucleotides. The second group is characterized by chromosomal deletions or uniparental disomies. Lissencephaly and the Miller-Dieker syndrome, Prader-Willi and Angelman syndromes and Duchenne and Becker muscular dystrophies belong to this category. The third group includes those neurogenetic disorders that are mainly caused by point mutations such as the X-linked leukodystrophies, including Pelizaeus-Merzbacher disease and adrenoleukodystrophy, Charcot-Marie-Tooth syndrome type 1, familial forms of amyotrophic lateral sclerosis, several types of craniosynostoses and some CNS tumor syndromes. Finally, Alzheimer's and Parkinson's disease are discussed as representatives of group four, i.e. genetically heterogeneous neurological disorders.
在过去几年中，分子神经遗传学已发展成为最具前景和活力的研究领域之一。这门新学科将现代分子遗传学技术应用于经典神经系统疾病的研究。在接下来的文章中，将介绍神经遗传疾病的定义，描述四类神经遗传疾病的分子基础，并展示近期的诊断进展。第一类疾病由三核苷酸扩增引起。直到大约三年前，人们还不知道“扩增”的三核苷酸重复序列会在任何物种中出现。如今，诸如亨廷顿舞蹈病、1型脊髓小脑共济失调、脆性X智力低下、延髓脊髓性肌萎缩和强直性肌营养不良等疾病都已知是由三核苷酸扩增引起的。第二类疾病的特征是染色体缺失或单亲二体。无脑回畸形和米勒 - 迪克尔综合征、普拉德 - 威利综合征和安吉尔曼综合征以及杜兴氏和贝克氏肌肉营养不良都属于这一类别。第三类包括那些主要由点突变引起的神经遗传疾病，如X连锁脑白质营养不良，包括佩利措伊斯 - 默茨巴赫病和肾上腺脑白质营养不良、1型夏科 - 马里 - 图斯综合征、家族性肌萎缩侧索硬化症、几种类型的颅缝早闭以及一些中枢神经系统肿瘤综合征。最后，将讨论阿尔茨海默病和帕金森病，作为第四类疾病的代表，即遗传异质性神经系统疾病。
