Genetics and Epidemiology of Essential Tremor

特发性震颤的遗传学和流行病学

• 批准号: 6468200
• 负责人: JOHN Ray GILBERT
• 金额: $ 36.16万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6468200
• 关键词: blood tests; family genetics; gene expression; gene mutation; genetic disorder; genetic disorder diagnosis; genetic markers; genotype; high performance liquid chromatography; human genetic material tag; human subject; linkage mapping; molecular cloning; nervous system disorder epidemiology; patient oriented research; polymerase chain reaction; questionnaires; single strand conformation polymorphism; tremor

Essential Tremor (ET) is a heterogenous tremor disorder characterized by a core group of features. The tremor syndrome is characterized by postural and kinetic tremor affecting the arms and hands, although the head, voice, and legs may also be affected. Although frequently described as a benign disorder, this is not true; many patients are socially and physically handicapped, with some patients being totally disabled. The differential diagnosis list for ET is extensive including dystonia, Parkinsonism, myoclonus, peripheral neuropathy, and other conditions. Prevalence estimates range widely, depending upon methodology and diagnostic criteria, from 0.003 to as high as 2% in the general population, with as much as 5% of the population affected over the age of 65. There are no known biological or diagnostic neuropathological markers for ET. The estimates of ET cases presenting with a positive family history range from 17.4% to 100%. Recent studies indicate that up to 96% of ET may be dominantly inherited. Clinical and genetic heterogeneity have slowed linkage studies. To date three loci associated with ET have been linked: 1) Familial Essential Tremor 1 (FET1) has been mapped in a series of Icelandic families on chromosome 3q13; (2) ETM mapped, in four unrelated US families, to chromosome 2p22-p25; and (3) a third locus maps, in a family that segregates both Parkinson's disease and postural tremor consistent with ET, to Chromosome 4p. We have, to date, ascertained, twelve ET and ET/PD linkage quality families. The largest pure ET kindred (DUK13001) have been excluded from known ET loci. The aims of this proposal are to ascertain and sample large families with ET, carry out a complete ET genome scan to establish linkage for these and additional ET families, identify new ET disease loci, and isolate and characterize ET genes, beginning with DUK13001 ET family.

特发性震颤 (ET) 是一种异质性震颤疾病，具有一组核心特征。震颤综合征的特征是影响手臂和手的姿势性和运动性震颤，尽管头部、声音和腿部也可能受到影响。虽然经常被描述为良性疾病，但事实并非如此。许多患者有社交和身体障碍，有些患者完全残疾。 ET 的鉴别诊断清单很广泛，包括肌张力障碍、帕金森病、肌阵挛、周围神经病和其他疾病。根据方法和诊断标准，患病率估计范围很广，一般人群中的患病率从 0.003% 到高达 2%，其中 65 岁以上人群中多达 5% 受影响。目前没有已知的 ET 生物学或诊断性神经病理学标志物。具有阳性家族史的 ET 病例估计范围为 17.4% 至 100%。最近的研究表明，高达 96% 的 ET 可能是显性遗传的。临床和遗传异质性减缓了连锁研究。迄今为止，与 ET 相关的三个基因座已被关联： 1) 家族性特发性震颤 1 (FET1) 已被定位在染色体 3q13 上的一系列冰岛家族中； (2) ETM 在四个不相关的美国家族中定位到染色体 2p22-p25； (3)第三个基因座定位于染色体4p，该基因座位于将帕金森病和与ET一致的姿势性震颤分开的家族中。迄今为止，我们已经确定了 12 个 ET 和 ET/PD 联动质量系列。最大的纯 ET 亲属 (DUK13001) 已被排除在已知的 ET 位点之外。该提案的目的是确定患有 ET 的大家族并对其进行抽样，进行完整的 ET 基因组扫描以建立这些和其他 ET 家族的联系，识别新的 ET 疾病位点，并从 DUK13001 ET 家族开始分离和表征 ET 基因。