Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS.
Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS.
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DOI：
10.1371/journal.pone.0075793
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Usami S
中科院分区：
文献类型：
--
作者：
Miyagawa M;Nishio SY;Ikeda T;Fukushima K;Usami S
遗传因素是重度至极重度听力损失最常见的病因，也是人工耳蜗植入 (CI) 和电声刺激 (EAS) 结果的关键决定因素之一。患有某些耳聋基因突变的患者接受 CI/EAS 后的令人满意的听觉表现表明，基因检测将有助于预测 CI/EAS 结果和决定治疗选择。然而，由于耳聋遗传的极端异质性，遗传信息的临床应用仍然存在困难。使用大规模并行 DNA 测序的目标外显子测序是一种新的强大策略，可发现耳聋等孟德尔疾病的罕见致病基因。我们对 58 个目标候选基因的外显子进行了大规模测序，分析了 8 名（4 名早发、4 名晚发）日本 CI/EAS 患者，这些患者的常见基因没有突变，包括 GJB2、SLC26A4 或线粒体 1555A>G 或 3243A>G 突变。我们成功地在四名患者的 MYO15A、TECTA、TMPRSS3 和 ACTG1 基因中发现了四种罕见的致病突变，这些患者在 CI（包括 EAS）中表现出相对较好的听觉表现，这表明基因检测可能能够预测植入后的表现。
Genetic factors, the most common etiology in severe to profound hearing loss, are one of the key determinants of Cochlear Implantation (CI) and Electric Acoustic Stimulation (EAS) outcomes. Satisfactory auditory performance after receiving a CI/EAS in patients with certain deafness gene mutations indicates that genetic testing would be helpful in predicting CI/EAS outcomes and deciding treatment choices. However, because of the extreme genetic heterogeneity of deafness, clinical application of genetic information still entails difficulties. Target exon sequencing using massively parallel DNA sequencing is a new powerful strategy to discover rare causative genes in Mendelian disorders such as deafness. We used massive sequencing of the exons of 58 target candidate genes to analyze 8 (4 early-onset, 4 late-onset) Japanese CI/EAS patients, who did not have mutations in commonly found genes including GJB2, SLC26A4, or mitochondrial 1555A>G or 3243A>G mutations. We successfully identified four rare causative mutations in the MYO15A, TECTA, TMPRSS3, and ACTG1 genes in four patients who showed relatively good auditory performance with CI including EAS, suggesting that genetic testing may be able to predict the performance after implantation.
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影响因子：
56.9
作者：
Wang, AH;Liang, Y;Friedman, TB
通讯作者：
Friedman, TB
影响因子：
1.4
作者：
Usami S;Miyagawa M;Nishio SY;Moteki H;Takumi Y;Suzuki M;Kitano Y;Iwasaki S
通讯作者：
Iwasaki S
影响因子：
46.9
作者：
Loman, Nicholas J.;Misra, Raju V.;Pallen, Mark J.
通讯作者：
Pallen, Mark J.
DOI：
10.1073/pnas.2334417100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Belyantseva, IA;Boger, ET;Friedman, TB
通讯作者：
Friedman, TB
DOI：
10.1007/s10162-011-0282-3
发表时间：
2011-12
影响因子：
2.4
作者：
Weegerink, Nicole J. D.;Schraders, Margit;Oostrik, Jaap;Huygen, Patrick L. M.;Strom, Tim M.;Granneman, Susanne;Pennings, Ronald J. E.;Venselaar, Hanka;Hoefsloot, Lies H.;Elting, Mariet;Cremers, Cor W. R. J.;Admiraal, Ronald J. C.;Kremer, Hannie;Kunst, Henricus P. M.
通讯作者：
Kunst, Henricus P. M.