A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings.
A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings.
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一个新型的WFS1突变，具有正常的VEMP和ECOCHG发现，具有主要的低频感官听力丧失。
DOI：
10.1186/1471-2350-9-48
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发表时间：
2008-06-02
影响因子：
--
通讯作者：
Street, Valerie A.
中科院分区：
文献类型：
--
作者：
Bramhall, Naomi F.;Kallman, Jeremy C.;Verrall, Aimee M.;Street, Valerie A.
低频感音神经性听力损失（LFSNHL）是一种罕见的临床表现。已知三种不同的已鉴定基因（DIAPH 1、MYO 7A和WFS 1）内的突变会导致LFSNHL。大多数遗传性LFSNHL与WFS 1基因（钨蛋白）的杂合突变相关。本研究的目的是使用遗传分析来确定一个小的美国家庭的遗传性LFSNHL是否与WFS 1基因的突变有关，并使用VEMP和EcochG测试来进一步表征该家庭的听前庭表型。美国家庭的临床表型的特点是听力学测试，前庭诱发肌源性电位（VEMP），耳蜗电图（EcochG）的评价。通过微卫星分析和WFS 1的直接测序进行遗传表征以用于突变检测。WFS 1基因的序列分析揭示了c.2054G>C处的一个新的杂合突变，预测Wolframin中的p.R685P氨基酸取代。c.2054G>C突变在家族中与听力损失忠实分离，并且在230条对照染色体中缺失。p.R685残基位于钨蛋白的亲水性C-末端内，并且在物种间是保守的。在分离WFS 1 c.2054G>C突变的个体中，VEMP和EcochG结果正常。我们在WFS 1的外显子8中发现了一种新的杂合错义突变，该突变预测了一种p.R685P氨基酸取代，这种取代可能是美国家族LFSNHL表型的基础。对于第一次，我们描述了VEMP和EcochG的结果分离杂合WFS 1突变的个人。
Low frequency sensorineural hearing loss (LFSNHL) is an uncommon clinical finding. Mutations within three different identified genes (DIAPH1, MYO7A, and WFS1) are known to cause LFSNHL. The majority of hereditary LFSNHL is associated with heterozygous mutations in the WFS1 gene (wolframin protein). The goal of this study was to use genetic analysis to determine if a small American family's hereditary LFSNHL is linked to a mutation in the WFS1 gene and to use VEMP and EcochG testing to further characterize the family's audiovestibular phenotype. The clinical phenotype of the American family was characterized by audiologic testing, vestibular evoked myogenic potentials (VEMP), and electrocochleography (EcochG) evaluation. Genetic characterization was performed by microsatellite analysis and direct sequencing of WFS1 for mutation detection. Sequence analysis of the WFS1 gene revealed a novel heterozygous mutation at c.2054G>C predicting a p.R685P amino acid substitution in wolframin. The c.2054G>C mutation segregates faithfully with hearing loss in the family and is absent in 230 control chromosomes. The p.R685 residue is located within the hydrophilic C-terminus of wolframin and is conserved across species. The VEMP and EcochG findings were normal in individuals segregating the WFS1 c.2054G>C mutation. We discovered a novel heterozygous missense mutation in exon 8 of WFS1 predicting a p.R685P amino acid substitution that is likely to underlie the LFSNHL phenotype in the American family. For the first time, we describe VEMP and EcochG findings for individuals segregating a heterozygous WFS1 mutation.
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影响因子：
2.9
作者：
JONES, DT;TAYLOR, WR;THORTON, JM
通讯作者：
THORTON, JM
影响因子：
30.8
作者：
Inoue, H;Tanizawa, Y;Permutt, MA
通讯作者：
Permutt, MA
影响因子：
5.6
作者：
Jones, DT
通讯作者：
Jones, DT
影响因子：
5.8
作者：
Jones, David T.
通讯作者：
Jones, David T.
影响因子：
3.5
作者：
Bespalova, IN;Van Camp, G;Lesperance, MM
通讯作者：
Lesperance, MM