WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis.
WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis.
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DOI：
10.1371/journal.pone.0193359
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Usami SI
中科院分区：
文献类型：
--
作者：
Kobayashi M;Miyagawa M;Nishio SY;Moteki H;Fujikawa T;Ohyama K;Sakaguchi H;Miyanohara I;Sugaya A;Naito Y;Morita SY;Kanda Y;Takahashi M;Ishikawa K;Nagano Y;Tono T;Oshikawa C;Kihara C;Takahashi H;Noguchi Y;Usami SI
Wolfram综合征1型基因（WFS 1）的杂合突变导致常染色体显性遗传性非综合征性遗传性听力损失，DFNA 6/14/38或Wolfram样综合征。到目前为止，已经报道了40多种不同的突变与DFNA 6/14/38有关。在本研究中，在大量日本听力损失（HL）患者中筛选了WFS 1变体，以阐明DFNA 6/14/38和Wolfram样综合征的患病率和临床特征。在2，549例无关的日本HL患者中对68个靶基因进行了大规模平行DNA测序，以确定导致HL的基因组变异。从病历中收集并分析WFS 1变异患者的详细临床特征。我们在19名先证者中成功鉴定了13种WFS 1变异体：其中8种是先前报道的突变，包括已知引起Wolfram样综合征的3种突变（p.A684V、p.K836N和p.E864K），5种是新突变。在602个常染色体显性遗传或线粒体HL家族中的15个先证者（2.5%）中检测到变异，在559个散发病例中的4个先证者（0.7%）中检测到变异;然而，在其他1，388个常染色体隐性遗传或未知家族史的先证者中未检测到变异。在30个人拥有的变体，显着的变化，观察到HL的发病以及在进行性HL和耳鸣的存在。前庭症状，这是很少报告，目前在7个30（23%）的受影响的个人。最普遍的听力配置是低频型，然而，一些人有高频HL。单倍型分析表明，p.A716T、p.K836T和p.E864K突变发生在这些突变热点上。本研究为WFS 1突变患者的听前庭表型提供了新的见解。
A heterozygous mutation in the Wolfram syndrome type 1 gene (WFS1) causes autosomal dominant nonsyndromic hereditary hearing loss, DFNA6/14/38, or Wolfram-like syndrome. To date, more than 40 different mutations have been reported to be responsible for DFNA6/14/38. In the present study, WFS1 variants were screened in a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA6/14/38 and Wolfram-like syndrome. Massively parallel DNA sequencing of 68 target genes was performed in 2,549 unrelated Japanese HL patients to identify genomic variations responsible for HL. The detailed clinical features in patients with WFS1 variants were collected from medical charts and analyzed. We successfully identified 13 WFS1 variants in 19 probands: eight of the 13 variants were previously reported mutations, including three mutations (p.A684V, p.K836N, and p.E864K) known to cause Wolfram-like syndrome, and five were novel mutations. Variants were detected in 15 probands (2.5%) in 602 families with presumably autosomal dominant or mitochondrial HL, and in four probands (0.7%) in 559 sporadic cases; however, no variants were detected in the other 1,388 probands with autosomal recessive or unknown family history. Among the 30 individuals possessing variants, marked variations were observed in the onset of HL as well as in the presence of progressive HL and tinnitus. Vestibular symptoms, which had been rarely reported, were present in 7 out of 30 (23%) of the affected individuals. The most prevalent audiometric configuration was low-frequency type; however, some individuals had high-frequency HL. Haplotype analysis in three mutations (p.A716T, p.K836T, and p.E864K) suggested that the mutations occurred at these mutation hot spots. The present study provided new insights into the audiovestibular phenotypes in patients with WFS1 mutations.
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影响因子：
5.2
作者：
Domènech, E;Gómez-Zaera, M;Nunes, V
通讯作者：
Nunes, V
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
2
作者：
Hildebrand, Michael S.;Sorensen, Jessica L.;Stnith, Richard J. H.
通讯作者：
Stnith, Richard J. H.
影响因子：
30.8
作者：
Inoue, H;Tanizawa, Y;Permutt, MA
通讯作者：
Permutt, MA