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: 6548727
• 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/6548727
• 关键词: calcium channel; cerebellar ataxia /dyskinesia; clinical research; degenerative motor system disease; family genetics; fibrous protein; gene mutation; genetic polymorphism; genetic screening; genetic susceptibility; genotype; hereditary peripheral nervous system disorder; human subject; human tissue; interview; malignant hyperthermia; neurogenetics; neuromuscular disorder; paraplegia; phenotype; questionnaires; scrapie; spastic paralysis; spongiform encephalopathy; tissue /cell culture

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: A clinically and pathologically distinct type of cardioskeletal myopathy is associated with mutations in the desmin gene: eleven novel causative mutations have now been identified and described, and adverse effects of each mutation tested in a cell culture expression system. An extremely aggressive variant of malignant hyperthermia was characterized in large North and South American families. It was linked to a novel mutation in the ryanodine receptor (RYR1) gene. A new study shows that worldwide distribution of hereditary Creutzfeldt-Jakob disease/Fatal Insomnia associated with the PRNP D178N mutation depends on recurrent mutations rather than founder effect. Genetic susceptibility to kuru and new variant Creutzfeldt-Jakob disease is tightly linked to a M/V polymorphism in the PRNP gene. Based on these data, a model have been developed that helps to determine the dynamics of the nvCJD epidemic in the UK and predict its outcome.

临床神经遗传学单位研究计划的重点是识别和表征基因和遗传机制涉及遗传性a）运动障碍，B）神经肌肉疾病，和c）朊病毒疾病。主要发现：一种临床和病理上不同类型的心脏骨骼肌病与结蛋白基因突变相关：现已鉴定和描述了11种新的致病突变，并在细胞培养表达系统中测试了每种突变的不良反应。一种恶性高热的极端侵袭性变体在北美和南美的大家庭中具有特征。它与ryanodine受体（RYR 1）基因中的一种新突变有关。一项新的研究表明，与PRNP D178 N突变相关的遗传性Creutzfeldt-Jakob病/致命性遗传病的全球分布取决于复发性突变，而不是创始人效应。库鲁病和新变异型克雅氏病的遗传易感性与PRNP基因的M/V多态性密切相关。基于这些数据，已经开发了一个模型，有助于确定在英国的nvCJD流行的动态，并预测其结果。