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研究计划的重点是鉴定和表征与遗传运动障碍和神经肌肉疾病有关的基因和遗传机制。主要发现：我们已经确定并表征了一组新的患者，其中肌原纤维肌病与Myotilin（Myot）基因突变有关。我们概述了desminopathy的几种表型不同的变体。已经建立了临床综合征与Desmin基因中因果突变的位置和类型之间的相关性。分析了来自5个不相关家族的60名患者，分析了脊柱肌肉萎缩（DSMA-V）和2D型charcot-marie-tooth疾病（CMT2D）的临床/病理特征；提出了该疾病的诊断标准。我们描述了一种不寻常的形式的脊椎动物共济失调，模仿了克鲁特兹菲尔特 - jakob病。在两个大型美国家庭中，震颤 - 雷斯托尼亚类型的必需震颤类型与6p染色体上的7 cm基因座和11p染色体上的21 cm区域有关。确定的viliuisk脑脊髓炎患者显示出与疾病的临床表现相关的鞘内IgG合成的证据。我们最近确定，这些免疫球蛋白与单纯疱疹类型1和2强烈反应，这表明这些或相关病毒的病因学作用。