Chai Yongchuan, Pang Xiuhong, Chen Dongye, Li Lei, Chen Ying, Sun Lianhua, Wang Xiaowen, Wu Hao, Yang Tao
Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Am J Med Genet A. 2014 Dec;164A(12):3115-9. doi: 10.1002/ajmg.a.36785. Epub 2014 Sep 23.
Childhood hearing impairment (HI) is genetically heterogeneous. Compared with the severe-to-profound HI, the molecular etiology of mild-to-moderate HI in children has been less well characterized, especially for those not inherited in the dominant mode. In this study, we recruited 114 probands with non-dominant, non-syndromic, mild-to-moderate childhood HI. Sequencing of GJB2, SLC26A4, and MTRNR1 identified causative mutations in 30.7% (35/114), 4.4% (5/114), and 4.4% (5/114) of subjects, respectively. A majority (62.9%) of bi-allelic GJB2 mutations have non-truncating mutations in at least one allele. In 10 multiplex probands with no GJB2, SLC26A4, and MTRNR1 mutations identified, targeted next-generation sequencing (NGS) of 79 known deafness genes did not identify any additional causes. Our data showed that the molecular etiology of mild-to-moderate childhood HI is considerably different from what reported for severe-to-profound HI and far from complete for those inherited in non-dominant modes.
儿童听力障碍（HI）具有遗传异质性。与重度至极重度HI相比，儿童轻度至中度HI的分子病因学特征尚不明确，尤其是那些非显性遗传模式的病例。在本研究中，我们招募了114名非显性、非综合征性、轻度至中度儿童HI先证者。对GJB2、SLC26A4和MTRNR1进行测序，分别在30.7%（35/114）、4.4%（5/114）和4.4%（5/114）的受试者中发现了致病突变。大多数（62.9%）双等位基因GJB2突变在至少一个等位基因中具有非截断突变。在10个未发现GJB2、SLC26A4和MTRNR1突变的多重先证者中，对79个已知耳聋基因进行靶向二代测序（NGS）未发现任何其他病因。我们的数据表明，轻度至中度儿童HI的分子病因学与重度至极重度HI报道的情况有很大不同，对于非显性遗传模式的病例，其分子病因学远未完全明确。
