Genotype-Phenotype Correlations In Movement and Neuromus

运动和神经肌肉的基因型-表型相关性

• 批准号: 7143885
• 负责人: Lev G Goldfarb
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7143885
• 关键词: Herpes simplex disease; abnormal involuntary movement; calcium channel; cerebellar ataxia /dyskinesia; congenital neuromuscular disorder; degenerative motor system disease; disease /disorder etiology; dystonia; encephalomyelitis; genetic disorder; genetic mapping; genetic markers; genetic polymorphism; genetic screening; genetic susceptibility; hereditary motor and sensory neuropathy; hereditary peripheral nervous system disorder; human subject; immunoglobulin G; malignant hyperthermia; neurogenetics; patient oriented research; spastic paralysis; spongiform encephalopathy; tremor

The Clinical Neurogenetics Unit research program is focused on identification and characterization of genes and genetic mechanisms involved in hereditary movement disorders and neuromuscular disorders. Major findings: We have identified and characterized a new group of patients in which Myofibrillar myopathy was associated with mutations in Myotilin (MYOT) gene. We outlined several phenotypically distinct variants of desminopathy; a correlation between the clinical syndrome and the position and type of the causative mutation in the desmin gene have been established. Clinical/pathological characteristics of spinal muscular atrophy (dSMA-V) and type 2D of Charcot-Marie-Tooth disease (CMT2D) were analysed in 60 patients from 5 unrelated families; diagnostic criteria for this disorder were proposed. We described an unusual form of spinocerebellar ataxia type 17 mimicking Creutzfeldt-Jakob disease. Tremor-dystonia type of essential tremor in two large American families was shown to be linked to a 7 cM locus on chromosome 6p and 21 cM region on chromosome 11p. Patients with definite Viliuisk encephalomyelitis show evidence for intrathecal IgG synthesis correlating with the clinical manifestations of the disease; we have recently established that these immunoglobulins strongly react with Herpes simplex type 1 and 2, suggesting an etiological role for these or related viruses.

临床神经遗传学单元的研究项目专注于遗传性运动障碍和神经肌肉疾病相关基因和遗传机制的识别和表征。主要发现：我们已经确定并描述了一组新的患者，其中肌原纤维肌病与肌动蛋白 (MYOT) 基因突变相关。我们概述了结线病的几种表型不同的变体；临床综合征与结蛋白基因致病突变的位置和类型之间的相关性已经建立。分析了来自5个无关家族的60名患者的脊髓性肌萎缩症（dSMA-V）和2D型夏科-马里-图思病（CMT2D）的临床/病理特征；提出了该疾病的诊断标准。我们描述了一种罕见的 17 型脊髓小脑共济失调，类似于克雅氏病。美国两个大家族中的震颤-肌张力障碍型特发性震颤被证明与 6p 染色体上的 7 cM 基因座和 11p 染色体上的 21 cM 区域有关。患有明确 Viliuisk 脑脊髓炎的患者显示出鞘内 IgG 合成与该疾病的临床表现相关的证据；我们最近确定这些免疫球蛋白与 1 型和 2 型单纯疱疹病毒发生强烈反应，表明这些病毒或相关病毒具有病原学作用。