Genetics and Epidemiology of Essential Tremor

特发性震颤（ET）是一种异质性震颤障碍，其特征在于一组核心特征。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。尽管经常被描述为良性疾病，但事实并非如此;许多患者在社交和身体方面有障碍，有些患者甚至完全残疾。ET的鉴别诊断列表是广泛的，包括肌张力障碍、帕金森综合征、肌阵挛、周围神经病变和其他病症。根据方法和诊断标准，患病率估计值范围很广，在一般人群中从0.003%到高达2%，65岁以上受影响的人群高达5%。没有已知的ET生物学或诊断神经病理学标志物。有阳性家族史的ET病例估计数为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。到目前为止，与ET相关的三个基因座已经被连锁：1）家族性特发性震颤1（FET 1）已经在一系列冰岛家族中定位在染色体3q 13上;（2）ETM在四个不相关的美国家族中定位在染色体2 p22-p25上;（3）第三个基因座在一个分离帕金森病和与ET一致的姿势性震颤的家族中定位在染色体4p上。到目前为止，我们已经确定了12个ET和ET/PD连锁质量家族。最大的纯ET家族（DUK 13001）已被排除在已知的ET基因座之外。该提案的目的是确定和采样大家庭与ET，进行一个完整的ET基因组扫描，以建立这些和其他ET家庭的联系，确定新的ET疾病位点，并分离和表征ET基因，从DUK 13001 ET家庭开始。

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.