Molecular biology of neurological diseases with abnormality of central or peripheral nerve myelin

目的：1.应用微卫星多态DNA标记对中枢或外周神经髓鞘异常的神经系统疾病进行基因定位。对与PLP、P0或PMP22基因座连锁的神经系统疾病家系进行DNA测序。利用280(CA)重复微卫星标记对未与已知基因座连锁的家系进行连锁分析。连锁分析定位的基因克隆。结果：1.一种新型运动感觉神经病的致病基因定位于染色体3着丝粒区域。在该区域，患者染色体上5个标记的等位基因频率明显增加。D3S1591的一个等位基因在所有患者中都是相同的，但在对照人群中频率很低。这一发现表明在所有患者中存在连锁不平衡和该等位基因的共同起源。对其他与P0或PMP22基因座连锁的家族性疾病进行了聚合酶链式反应-单链构象多态性分析和DNA测序分析。目前已开始对与PLP、P0和PMP22基因座无连锁的中枢神经或周围神经异常的家族性疾病进行连锁分析。结论：在本研究项目中，我们发现了一种新的遗传性运动和感觉神经病。负责这一新疾病的基因克隆是下一步重要的研究项目。

Purpose :1. Gene mapping of neurological diseases with abnormality of central or peripheral nerve myelination using microsatellite polymorphic DNA markers.2. DNA sequencing of the families with neurological diseases linked to PLP, P0 or PMP22 gene locus.3. Linkage analysis of the families with no linkage to the known gene locus using 280 (CA) repeat microsatellite markers.4. Cloning of the genes mapped by the linkage analysis.Results :1. The gene responsible for a new type of motor and sensory neuropathy was mapped to chromosome 3 centromere region.2. In this region ; the patients'chromosomes showed an obvious increase in the allele frequency of five markers. One allele in D3S1591 was identical in all patients but had a low frequency in the control population. This finding suggested the presence of linkage disequilbrium and a common origin of this allele in all patients.3. Other familial disorders linked to P0 or PMP22 gene locus were analyzed by PCR-SSCP and DNA sequencing Linkage analysis of familial disorders with central or peripheral nerve abnormalities, which were not linked to PLP,P_0 and PMP22 gene loci, has been started. Conclusions : We identified a new type of hereditary motor and sensory neuropathy in this research project. Gene cloning responsible for this new disease is the important next research project.