Genetic causes of moderate to severe hearing loss point to modifiers.
Genetic causes of moderate to severe hearing loss point to modifiers.
复制标题
DOI：
10.1111/cge.12856
复制
发表时间：
2017-04
影响因子：
3.5
通讯作者：
Friedman TB
中科院分区：
文献类型：
--
作者：
Naz S;Imtiaz A;Mujtaba G;Maqsood A;Bashir R;Bukhari I;Khan MR;Ramzan M;Fatima A;Rehman AU;Iqbal M;Chaudhry T;Lund M;Brewer CC;Morell RJ;Friedman TB
隐性遗传的中度至重度感音神经性听力损失的遗传基础尚不清楚，尽管与重度耳聋相比，其患病率更高。我们招募了 92 个近亲家庭，将稳定或进行性、隐性遗传的中度或重度听力损失者分开。我们利用纯合性作图、桑格测序、通过大规模并行测序和全外显子组测序对已知耳聋基因进行靶向捕获，以确定这些家庭中听力损失的分子基础。在 69% 的参与家庭中发现了已知耳聋基因的变异体，其中 SLC26A4、GJB2、MYO15A、TMC1、TMPRSS3、OTOF、MYO7A 和 CLDN14 基因共同导致了 54% 家庭的听力损失。我们在 21 个已知的耳聋基因中鉴定出了 20 个已报告的变异和 21 个新的变异。先前与稳定、重度耳聋相关的 20 种变异中，有 16 种与我们家庭中的中度至重度或进行性听力损失相关。这些数据表明遗传背景、环境因素或两者在人类听力损失严重程度的调节因素中发挥着重要作用。
The genetic underpinnings of recessively inherited moderate to severe sensorineural hearing loss are not well understood, despite its higher prevalence in comparison to profound deafness. We recruited 92 consanguineous families segregating stable or progressive, recessively inherited moderate or severe hearing loss. We utilized homozygosity mapping, Sanger sequencing, targeted capture of known deafness genes with massively parallel sequencing and whole exome sequencing to identify the molecular basis of hearing loss in these families. Variants of the known deafness genes were found in 69% of the participating families with the SLC26A4, GJB2, MYO15A, TMC1, TMPRSS3, OTOF, MYO7A and CLDN14 genes together accounting for hearing loss in 54% of the families. We identified 20 reported and 21 novel variants in 21 known deafness genes. Sixteen of the twenty reported variants, previously associated with stable, profound deafness were associated with moderate to severe or progressive hearing loss in our families. These data point to a prominent role for genetic background, environmental factors or both as modifiers of human hearing loss severity.