MOLECULAR GENETICS OF INHERITED NEUROLOGIC AND PSYCHIATRIC DISORDERS

我们研究了导致基因突变的特征 通过研究基因遗传的神经或精神疾病 特定蛋白质的组织，这些蛋白质可能在 临床表现的发病机制。利用遗传的溶酶体 储存障碍、高谢病和法布里病作为模型，我们 证明了这些基因中所见的表型异质性 疾病是不同突变的结果，每种突变都会影响蛋白质 活跃性和影响加工、分隔和/或 蛋白质的稳定性。重组DNA技术已被用于 阐明参与这些过程的蛋白质的基因结构 精神错乱。限制性片段长度多态(RFLP)已经被 可用于高谢尔突变的鉴定 常见于神经病变表型的疾病。Northern印迹 分析提供了正常和突变的结构的进一步细节 基因。导致神经系统受累的分子机制 对这些疾病也进行了调查。这项研究的结果 应该为诊断和制定提供更合理的基础 这些遗传性疾病的治疗策略。

We approached the characterization of the mutations responsible for inherited neurological or psychiatric disorders by studying the gene organization of specific proteins that might have a role in the pathogenesis of the clinical manifestations. Using the inherited lysosomal storage disorders, Gaucher disease and Fabry disease, as models, we demonstrated that the phenotypic heterogeneity seen within these inherited disorders is a consequence of different mutations, each affecting protein activity and influencing the processing, compartmentalization and/or stability of the protein. Recombinant DNA techniques have been used to elucidate the structure of the gene for the proteins involved in these disorders. Restriction fragment length polymorphisms (RFLPs) have been identified that are useful for the identification of a mutation in Gaucher disease which frequently occurs in neuronopathic phenotypes. Northern blot analysis provides further details of the structure of the normal and mutant genes. The molecular mechanisms leading to nervous system involvement in these disorders have also been investigated. The results of this research should provide a more rational foundation for the diagnosis and formulation of therapeutic strategies for these inherited disorders.