title: Molecular etiology of non-dominant, non-syndromic, mild-to-moderate childhood hearing impairment in Chinese Hans.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yongchuan
authors.initials: Y
authors.lastname: Chai
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Pang
authors.forename: Dongye
authors.initials: D
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Lianhua
authors.initials: L
authors.lastname: Sun
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
mesh_terms: D044466:Asian People / Q000235:genetics*; D002648:Child; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26
keywords: deafness; genetic etiology; mild-to-moderate hearing loss; non-syndromic; target next-generation sequencing