Genotype-phenotype Correlations In Movement And Neuromus

临床神经遗传学单位的研究计划集中于与遗传性a)运动障碍、b)神经肌肉障碍和c)Pron疾病相关的基因和遗传机制的识别和表征。主要发现：现在已经鉴定和描述了22个结蛋白基因的致病突变，并在细胞培养表达系统中测试了每个突变的不良影响。已概述了几种临床和病理上不同的脱毛症变种。结蛋白基因突变的位置和类型与临床症状有一定的相关性。两种以前被认为是独立的疾病，5型远端脊髓性肌萎缩症(DSMA-V)和2D型Charcot-Marie-Tooth病(CMT2D)与相同GARS基因的突变有关，这表明这些疾病是等位基因，或者可能代表同一疾病，因为表型差异不显著。这一结论需要改变现有的周围神经病的分类。库鲁病和新变异的克雅氏病的遗传易感性与PRNP基因的M/V多态密切相关，这为预测与疯牛病相关的变异CJD流行的预期长度和规模提供了一个模型。在两个美国大家庭中，震颤-肌张力障碍型特发性震颤被证明与6p染色体上7 cM的位置和1p染色体上21 cM的区域相关联。明确的Viliuisk脑脊髓炎患者的鞘内免疫球蛋白合成与疾病的临床表现相关。寡克隆抗体检测可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.