Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WTS1
Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WTS1
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DOI：
10.1002/ajmg.a.32449
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发表时间：
2008-09-01
影响因子：
2
通讯作者：
Stnith, Richard J. H.
中科院分区：
文献类型：
--
作者：
Hildebrand, Michael S.;Sorensen, Jessica L.;Stnith, Richard J. H.
大多数常染色体显性遗传性低频感音神经性听力损失（LFSNHL）的家族性病例可归因于DFNA 6/14/38位点的Wolframin综合征1（WFS 1）基因突变。2001年，在6个LFSNHL分离家族中首次描述了该基因座的WFS 1突变，这些家族在2,000 Hz以下是非进行性的;致病突变都聚集在钨蛋白的C-末端结构域。WFS 1的突变也会导致Wolfram综合征（WS），这是一种常染色体隐性遗传的神经退行性疾病，由糖尿病，视神经萎缩和耳聋定义，而WTS 1中的许多单核苷酸多态性（SNP）与糖尿病，精神疾病和帕金森病的风险增加有关。本研究在一个分离的常染色体显性LFSNHL美国家庭中进行。两个听力受损的家庭成员也有自身免疫性疾病-格雷夫斯病（GD）和克罗恩病（CD）。基于低频音频图谱，完成了WTS 1的突变筛查，并发现了一个新的错义突变（c. 2576 G-> A），其导致精氨酸至谷氨酰胺的取代（p.R859Q），在钨蛋白的C-末端结构域中鉴定，其中大多数LFSNHL引起的突变聚集。GD家族成员还携带与其他自身免疫性疾病相关的WFS 1多态性。(C)2008 Wiley-Liss，Inc.
Most familial cases of autosomal dominant low frequency sensorineural hearing loss (LFSNHL) are attributable to mutations in the wolframin syndrome 1 (WFS1) gene at the DFNA6/14/38 locus. WFS1 mutations at this locus were first described in 2001 in six families segregating LFSNHL that was non-progressive below 2,000 Hz; the causative mutations all clustered in the C-terminal domain of the wolframin protein. Mutations in WFS1 also cause Wolfram syndrome (WS), an autosomal recessive neurodegenerative disorder defined by diabetes mellitus, optic atrophy and often deafness, while numerous single nucleotide polymorphisms (SNPs) in WTS1 have been associated with increased risk for diabetes mellitus, psychiatric illnesses and Parkinson disease. This study was conducted in an American family segregating autosomal dominant LFSNHL. Two hearing impaired family members also had autoimmune diseases-Graves disease (GD) and Crohn disease (CD). Based on the low frequency audioprofile, mutation screening of WTS1 was completed and a novel missense mutation (c. 2576G -> A) that results in an arginine-to-glutamine substitution (p.R859Q) was identified in the C-terminal domain of the wolframin protein where most LFSNHL-causing mutations cluster. The family member with GD also carried polymorphisms in WFS1 that have been associated with other autoimmune diseases. (C) 2008 Wiley-Liss, Inc.