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.

临床神经遗传学单位的研究计划侧重于遗传性运动障碍和神经肌肉障碍所涉及的基因和遗传机制的识别和表征。主要发现：我们已经确定并表征了一组新的患者，在这些患者中，肌原纤维肌病与Myotilin(MYOT)基因突变有关。我们概述了结缔组织病的几种不同的表型变异；已经建立了结蛋白基因致病突变的位置和类型与临床症状之间的相关性。本文分析了5个无关家系60例脊髓性肌萎缩症(DSMA-V)和2D型Charcot-Marie-Tooth病(CMT2D)的临床和病理特点，提出了诊断标准。我们描述了一种罕见的脊髓小脑性共济失调17型，类似于CreutzFeldt-Jakob病。在两个美国家系中发现的震颤-肌张力障碍型特发性震颤与染色体6p上的7 cM和11p上的21 cM区域连锁。明确的Viliuisk脑脊髓炎患者有证据表明鞘内免疫球蛋白合成与疾病的临床表现相关；我们最近证实这些免疫球蛋白与1型和2型单纯疱疹病毒强烈反应，提示这些或相关病毒的病因学作用。