Genotype-phenotype In Movement & Neuromuscular Disorders

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。已经概述了几种临床和病理上不同的神经鞘病变体：

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: Variant 1, uncomplicated progressive skeletal myopathy Variant 2, skeletal myopathy followed by cardiomyopathy Variant 3, skeletal myopathy followed by respiratory muscle involvement, but no cardiac disease Variant 4, cardiomyopathy followed by skeletal myopathy Variant 5, isolated cardiomyopathy 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.