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: 7324550
• 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/7324550
• 关键词: Genotype; Phenotype; Correlations; Movement; Neuromus

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研究计划的重点是鉴定和遗传运动障碍和神经肌肉疾病涉及的基因和遗传机制的特征。主要发现：我们发现并描述了一组新的肌纤原性肌病与肌动素（MYOT）基因突变相关的患者。我们概述了几种不同的神经鞘病的表型变体；临床综合征与致盲蛋白基因突变的位置和类型之间的相关性已经建立。分析来自5个无亲缘关系家庭的60例脊髓性肌萎缩症（dSMA-V）和腓骨肌萎缩症（CMT2D）的临床/病理特征；提出了这种疾病的诊断标准。我们描述了一个不寻常的形式脊髓小脑共济失调17型模拟克雅氏病。震颤-肌张力障碍型特发性震颤在两个美国大家族中被证明与6p染色体上的7 cM位点和11p染色体上的21 cM区域有关。明确的viluisk脑脊髓炎患者显示鞘内IgG合成的证据与疾病的临床表现相关；我们最近发现，这些免疫球蛋白与1型和2型单纯疱疹病毒有强烈反应，这表明这些病毒或相关病毒在病因学上起作用。