Genetics and Epidemiology of Essential Tremor

特发性震颤的遗传学和流行病学

• 批准号: 6710593
• 负责人: JOHN Ray GILBERT
• 金额: $ 36.58万
• 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/6710593
• 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）是一种具有一系列核心特征的异质性震颤疾病。震颤综合征的特征是影响手臂和手的体位性和动态性震颤，尽管头部、声音和腿部也可能受到影响。虽然经常被描述为一种良性疾病，但事实并非如此；许多患者在社交和身体上都有残疾，有些患者完全残疾。ET的鉴别诊断包括肌张力障碍、帕金森氏症、肌阵挛、周围神经病变和其他疾病。根据不同的方法和诊断标准，患病率估计值相差很大，一般人群的患病率从0.003%到高达2%，65岁以上人群的患病率高达5%。目前还没有已知的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病例的估计范围从17.4%到100%。最近的研究表明，高达96%的ET可能主要遗传。临床和遗传异质性延缓了相关研究。迄今为止，与ET相关的三个位点已被联系起来：1)家族性特发性震颤1 （FET1）已在一系列冰岛家族的染色体3q13上被定位；(2)在4个不相关的美国家族中，ETM定位于染色体2p22-p25；(3)在一个家族中，帕金森病和体位性震颤与ET相一致，第三个位点位于染色体4p上。到目前为止，我们已经确定了12个ET和ET/PD联动质量家族。最大的纯ET亲缘（DUK13001）已从已知的ET基因座中排除。本提案的目的是确定和取样ET大家族，进行完整的ET基因组扫描以建立这些家族和其他ET家族的联系，确定新的ET疾病位点，并从DUK13001 ET家族开始分离和表征ET基因。