当前位置: X-MOL 学术Genet. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
AUDIOME: a tiered exome sequencing-based comprehensive gene panel for the diagnosis of heterogeneous nonsyndromic sensorineural hearing loss.
Genetics in Medicine ( IF 8.8 ) Pub Date : 2018-Mar-29 , DOI: 10.1038/gim.2018.48
Qiaoning Guan 1 , Jorune Balciuniene 1 , Kajia Cao 1 , Zhiqian Fan 1 , Sawona Biswas 1 , Alisha Wilkens 1 , Daniel J Gallo 1 , Emma Bedoukian 2 , Jennifer Tarpinian 2 , Pushkala Jayaraman 1 , Mahdi Sarmady 1, 3 , Matthew Dulik 1, 3 , Avni Santani 1, 3 , Nancy Spinner 1, 3 , Ahmad N Abou Tayoun 1, 3 , Ian D Krantz 2, 4 , Laura K Conlin 1, 3 , Minjie Luo 1, 3
Affiliation  

PurposeHereditary hearing loss is highly heterogeneous. To keep up with rapidly emerging disease-causing genes, we developed the AUDIOME test for nonsyndromic hearing loss (NSHL) using an exome sequencing (ES) platform and targeted analysis for the curated genes.MethodsA tiered strategy was implemented for this test. Tier 1 includes combined Sanger and targeted deletion analyses of the two most common NSHL genes and two mitochondrial genes. Nondiagnostic tier 1 cases are subjected to ES and array followed by targeted analysis of the remaining AUDIOME genes.ResultsES resulted in good coverage of the selected genes with 98.24% of targeted bases at >15 ×. A fill-in strategy was developed for the poorly covered regions, which generally fell within GC-rich or highly homologous regions. Prospective testing of 33 patients with NSHL revealed a diagnosis in 11 (33%) and a possible diagnosis in 8 cases (24.2%). Among those, 10 individuals had variants in tier 1 genes. The ES data in the remaining nondiagnostic cases are readily available for further analysis.ConclusionThe tiered and ES-based test provides an efficient and cost-effective diagnostic strategy for NSHL, with the potential to reflex to full exome to identify causal changes outside of the AUDIOME test.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2018.48.

中文翻译:

AUDIOME:基于分层外显子组测序的综合基因组,用于诊断异质性非综合征感音神经性听力损失。

目的遗传性听力损失具有高度异质性。为了跟上迅速出现的致病基因,我们使用外显子组测序 (ES) 平台开发了针对非综合征性听力损失 (NSHL) 的 AUDIOME 测试,并对精选基因进行了靶向分析。方法针对该测试实施了分层策略。第 1 层包括对两个最常见的 NSHL 基因和两个线粒体基因的组合 Sanger 和靶向缺失分析。非诊断 1 级病例接受 ES 和阵列,然后对剩余的 AUDIOME 基因进行靶向分析。结果 ES 导致所选基因的良好覆盖率,98.24% 的目标碱基 > 15 ×。为覆盖较差的区域制定了填充策略,这些区域通常属于富含 GC 或高度同源的区域。对 33 名 NSHL 患者的前瞻性检测显示 11 名(33%)确诊,8 名(24.2%)可能确诊。其中,10 个人在 1 级基因中有变异。剩余非诊断病例中的 ES 数据可随时用于进一步分析。结论分层和基于 ES 的测试为 NSHL 提供了一种有效且具有成本效益的诊断策略,具有反射到全外显子组以识别 AUDIOME 之外的因果变化的潜力test.Genetics in Medicine Advance 在线出版物,2018 年 3 月 29 日;doi:10.1038/gim.2018.48。结论分层和基于 ES 的测试为 NSHL 提供了一种高效且具有成本效益的诊断策略,具有反射到全外显子组以识别 AUDIOME 测试之外的因果变化的潜力。医学遗传学提前在线出版,2018 年 3 月 29 日;doi:10.1038/gim.2018.48。结论分层和基于 ES 的测试为 NSHL 提供了一种高效且具有成本效益的诊断策略,具有反射到全外显子组以识别 AUDIOME 测试之外的因果变化的潜力。医学遗传学提前在线出版,2018 年 3 月 29 日;doi:10.1038/gim.2018.48。
更新日期:2018-03-30
down
wechat
bug