Genetics of essential tremor.
Genetics of essential tremor.
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DOI：
10.1016/s1353-8020(11)70043-8
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发表时间：
2012
影响因子：
4.1
通讯作者：
B. Jasińska‐Myga;C. Wider
中科院分区：
文献类型：
--
作者：
B. Jasińska‐Myga;C. Wider
特发性震颤（ET）是一种常见的疾病，表现为进行性动作震颤。虽然ET传统上被视为一种散发性疾病，但相当一部分病例报告了震颤的阳性家族史。常染色体显性遗传可在许多家庭中表现出来。以前，在家族中的全基因组连锁研究绘制了ET的三个位点，遗传性特发性震颤-1（ETM 1），ETM 2和ETM 3。然而，在这些基因座内的候选基因中没有复制因果突变，包括多巴胺D3受体（DRD 3）和HS 1结合蛋白3（HS 1BP 3）。最近，第一个全基因组关联研究ET随后在不同人群中进行的复制研究确定了富含亮氨酸的重复序列和含有IG结构域的1个基因（LINGO 1）SNP rs 9652490与ET风险之间的显著关联。考虑到ET作为一种复杂性状可能受到罕见变异的综合影响的可能性，对整个基因组（外显子组测序）或整个基因组（基因组测序）的所有外显子进行测序的新型高通量技术可能在理解/破译ET的遗传背景方面变得至关重要。
Essential tremor (ET) is a prevalent condition manifesting with progressive action tremor. Although ET was traditionally viewed as a sporadic disease, a significant proportion of cases report a positive family history of tremor. Autosomal dominant inheritance can be demonstrated in many families. Previously, genome-wide linkage studies in families mapped three loci for ET, hereditary essential tremor-1 (ETM1), ETM2 and ETM3. However, no causal mutation has been replicated in candidate genes within these loci, including dopamine D3 receptor (DRD3) and HS1-binding protein 3 (HS1BP3). Recently, the first genome-wide association study in ET followed by replication studies conducted in diverse populations identified a significant association between the leucine-rich repeat and Ig domain containing 1 gene (LINGO1) SNP rs9652490 and risk for ET Although further novel variants were indentified in LINGO1 and its paralog LINGO2 that may be associated with risk for ET, the pathogenic mechanisms involved remain elusive. Given the possibility that ET as a complex trait may be influenced by the combined effects of rare variants, novel high-throughput technologies sequencing all exons across the genome (exome sequencing) or the whole genome (genome sequencing) may become crucial in understanding/deciphering the genetic background of ET.