Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families.
Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families.
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DOI：
10.1186/1750-1172-7-60
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发表时间：
2012-09-03
影响因子：
3.7
通讯作者：
Lee SH
中科院分区：
文献类型：
--
作者：
Baek JI;Oh SK;Kim DB;Choi SY;Kim UK;Lee KY;Lee SH
遗传性听力损失是最常见的异质性疾病之一，已经在60多个基因中发现了可导致听力损失的遗传变异。这些听力损失基因中的大多数已经使用经典的遗传学方法检测到，通常从遗传性听力损失大家族的连锁分析开始。然而，这些经典的策略不太适合在较小的家庭谁没有足够的遗传信息的突变分析。在8个韩国常染色体显性遗传非综合征型感音神经性听力损失家系中，选择80个已知的听力损失基因，并通过靶向下一代测序（NGS）进行同步测序。在5个不同的基因（ACTG1、MYO1F、DIAPH1、POU4F3和EYA 4）中发现了5个已知的听力损失基因突变，包括1个无义突变和4个错义突变，这些突变的基因型与每个家族中听力损失的常染色体显性遗传模式一致。在这些韩国家庭中没有发现突变热点。靶向NGS允许检测受影响个体中的致病性突变，这些个体不是经典遗传学研究的候选人。这份报告是第一份记录有效使用NGS技术检测东亚人群听力损失的致病性突变的报告。利用该NGS技术建立韩国听力损失患者常见突变数据库并进一步积累数据，将有助于遗传性听力损失的早期诊断和基础治疗。
Hereditary hearing loss is one of the most common heterogeneous disorders, and genetic variants that can cause hearing loss have been identified in over sixty genes. Most of these hearing loss genes have been detected using classical genetic methods, typically starting with linkage analysis in large families with hereditary hearing loss. However, these classical strategies are not well suited for mutation analysis in smaller families who have insufficient genetic information. Eighty known hearing loss genes were selected and simultaneously sequenced by targeted next-generation sequencing (NGS) in 8 Korean families with autosomal dominant non-syndromic sensorineural hearing loss. Five mutations in known hearing loss genes, including 1 nonsense and 4 missense mutations, were identified in 5 different genes (ACTG1, MYO1F, DIAPH1, POU4F3 and EYA4), and the genotypes for these mutations were consistent with the autosomal dominant inheritance pattern of hearing loss in each family. No mutational hot-spots were revealed in these Korean families. Targeted NGS allowed for the detection of pathogenic mutations in affected individuals who were not candidates for classical genetic studies. This report is the first documenting the effective use of an NGS technique to detect pathogenic mutations that underlie hearing loss in an East Asian population. Using this NGS technique to establish a database of common mutations in Korean patients with hearing loss and further data accumulation will contribute to the early diagnosis and fundamental therapies for hereditary hearing loss.
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DOI：
10.1016/j.ijporl.2008.05.007
发表时间：
2008-09-01
影响因子：
1.5
作者：
Lee, K. Y.;Choi, S. Y.;Lee, S. H.
通讯作者：
Lee, S. H.
影响因子：
3.9
作者：
Collin, Rob W. J.;Chellappa, Ramesh;Kremer, Hannie
通讯作者：
Kremer, Hannie
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。
影响因子：
--
作者：
Bramhall, Naomi F.;Kallman, Jeremy C.;Verrall, Aimee M.;Street, Valerie A.
通讯作者：
Street, Valerie A.
影响因子：
120.7
作者：
Green, GE;Scott, DA;Smith, RJH
通讯作者：
Smith, RJH
影响因子：
3.5
作者：
Denoyelle, F;Weil, D;Petit, C
通讯作者：
Petit, C