Genotype-phenotype Correlations In Movement And Neuromus

临床神经遗传学单位研究项目的重点是识别和表征遗传基因和遗传机制涉及a)运动障碍，b)神经肌肉疾病，和c)朊病毒疾病。主要发现：目前已鉴定和描述了22种致盲蛋白基因突变，并在细胞培养表达系统中测试了每种突变的不良影响。几种临床和病理上不同的神经鞘病已被概述。致盲蛋白基因突变的位置和类型与临床证候有相关性。之前被认为是独立的两种疾病，5型远端脊髓性肌萎缩症（dSMA-V）和2D型腓骨肌萎缩症（CMT2D）与同一GARS基因的突变有关，这表明这些疾病是等位基因，或者可能代表相同的疾病，因为表型差异不显著。这一结论要求改变现有的周围神经病变分类。库鲁病和新型克雅氏病的遗传易感性与PRNP基因的M/V多态性密切相关，这为预测与疯牛病相关的变异型克雅氏病流行的预期长度和大小提供了一个模型。震颤-肌张力障碍型特发性震颤在两个美国大家族中被证明与染色体6p上的7 cM位点和染色体1p上的21 cM区域有关。明确的viluisk脑脊髓炎患者显示鞘内IgG合成的证据与疾病的临床表现相关。寡克隆IgG条带检测将作为一种有价值的诊断方法。

The Clinical Neurogenetics Unit research program is focused on identification and characterization of genes and genetic mechanisms involved in hereditary a) movement disorders, b) neuromuscular disorders, and c) prion diseases. Major findings: Twenty-two causative mutations in the desmin gene have now been identified and described, and adverse effects of each mutation tested in a cell culture expression system. Several clinically and pathologically distinct variants of desminopathy have been outlined. There is a correlation between the clinical syndromes and the position and type of the causative mutation in the desmin gene. Two disorders previously considered to be independent, type 5 of distal spinal muscular atrophy (dSMA-V) and type 2D of Charcot-Marie-Tooth disease (CMT2D) are associated with mutations in the same GARS gene, suggesting that these disorders are allelic, or perhaps represent the same disease, since phenotypic differences are not significant. This conclusion requires changes in the existing classification of peripheral neuropathies. Genetic susceptibility to kuru and new variant Creutzfeldt-Jakob disease is tightly linked to a M/V polymorphism in the PRNP gene, providing a model for predictions of the expected length and size of the developing epidemic of variant CJD associated with mad cow disease. Tremor-dystonia type of essential tremor in two large American families is shown to be linked to a 7 cM locus on chromosome 6p and a 21 cM region on chromosome 1p. Patients with definite Viliuisk encephalomyelitis show evidence for intrathecal IgG synthesis correlating with the clinical manifestations of the disease. The detection of oligoclonal IgG banding will be used as a valuable diagnostic assay.