title: Exome sequencing identifies POU4F3 as the causative gene for a large Chinese family with non-syndromic hearing loss.
abstract: Hearing impairment, or deafness (in its most severe form), is one of the most common human sensory disorders. There have been several reports of autosomal dominant mutations in the POU4F3 gene, which is associated with non-syndromic hearing loss. In this study, we identified a novel heterozygous mutation (c.602delT, p.L201fs) in the gene POU4F3 by taking advantage of whole-exome sequencing, which was validated by Sanger sequencing and completely co-segregated within a large hearing impaired Chinese family. We have focused on this pedigree since 2002, and we have mapped a deafness locus named DFNA42 (which has been renamed DFNA52, OMIM entry 607683) via a genome-wide scan. Furthermore, we analyzed this mutational variant and found that it was located at the beginning of the first functional domain of POU4F3, which could theoretically impair the function of POU4F3. We have identified a novel frameshift mutation in the POU4F3 gene. Further functional studies of variants of this specific gene are needed to illustrate the pathogenic mechanism(s) that underlie hearing impairment.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.|State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Xin Zhang
authors.initials: XZ
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Chu Feng
authors.initials: CF
authors.lastname: He
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.|State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.|School of Biological Science and Technology, Central South University, Changsha, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Xue Zhong
authors.initials: XZ
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Ling Yun
authors.initials: LY
authors.lastname: Mei
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.|School of Biological Science and Technology, Central South University, Changsha, China.
authors.forename: Zheng Mao
authors.initials: ZM
authors.lastname: Hu
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D059472:Exome / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D010375:Pedigree; D017422:Sequence Analysis, DNA; D050821:Transcription Factor Brn-3C / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C111223:POU4F3 protein, human; D050821:Transcription Factor Brn-3C