An Examination of KCNE1 Mutations and Common Variants in Chronic Tinnitus.
An Examination of KCNE1 Mutations and Common Variants in Chronic Tinnitus.
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DOI：
10.3390/genes1010023
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发表时间：
2010-04-28
期刊：
影响因子：
3.5
通讯作者：
Langguth B
中科院分区：
文献类型：
--
作者：
Sand PG;Luettich A;Kleinjung T;Hajak G;Langguth B
慢性耳鸣是一种非常普遍的，往往使人丧失能力的条件，往往与感音神经性听力损失。虽然它的病因仍然不完全了解，但人们越来越意识到遗传因素易患或加重慢性耳鸣。这种疾病的候选基因包括KCNE1，这是一种钾通道亚基基因，与中央前庭神经元的成熟缺陷、梅尼埃病和噪声引起的听力损失有关。对201例诊断为慢性耳鸣的高加索门诊患者进行了系统的KCNE 1开放阅读框突变筛查，并通过直接测序法对相邻序列进行了突变筛查。确定了46个已知变异体的等位基因频率，加上两个新的KCNE1突变。这些包括在编码KCNE1跨膜结构域的高度保守区域中的一个错义取代（V47 I），以及在该基因的3'UTR中的一个罕见变体。当假设次要等位基因占主导地位对基因型进行分组时，没有观察到基因型或复合基因型对耳鸣严重程度的显着影响。新发现的V47I替代支持听力障碍中突变谱的扩大。然而，关于早期研究中健康对照人群的等位基因频率，更常见的KCNE1变体不太可能在慢性耳鸣中起主要作用。进一步的调查被邀请来解决其他通道亚基的变化作为耳鸣的可能危险因素。
Chronic tinnitus is a highly prevalent and often incapacitating condition frequently associated with sensorineural hearing loss. While its etiology remains incompletely understood there is a growing awareness of genetic factors that predispose to, or aggravate chronic tinnitus. Candidate genes for the disorder include KCNE1, a potassium channel subunit gene that has been implicated in maturation defects of central vestibular neurons, in Menière's disease, and in noise-induced hearing loss. 201 Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCNE1 open reading frame and in the adjacent sequence by direct sequencing. Allele frequencies were determined for 46 known variants, plus two novel KCNE1 mutations. These comprised one missense substitution (V47I) in the highly conserved region encoding the KCNE1 transmembrane domain, and one rare variant in the gene's 3'UTR. When genotypes were grouped assuming dominance of the minor alleles, no significant genotype or compound genotype effects were observed on tinnitus severity. The newly identified V47I substitution argues in favor of an enlarged spectrum of mutations in hearing disorders. However, with regard to allele frequencies in healthy control populations from earlier studies, more common KCNE1 variants are unlikely to play a major role in chronic tinnitus. Further investigations are invited to address variation in additional channel subunits as possible risk factors in tinnitus.
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影响因子：
3.7
作者：
Clancy SM;Chen B;Bertaso F;Mamet J;Jegla T
通讯作者：
Jegla T
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5.5
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3.4
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Haaf T
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5.2
作者：
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