title: A dominant variant in DMXL2 is linked to nonsyndromic hearing loss.
abstract: To explore the genetic etiology of deafness in a dominant family with late-onset, progressive, nonsyndromic hearing loss.
  
  
  
  Genome-wide linkage analysis was performed for 21 family members. Candidate pathogenic variants were identified by whole-exome sequencing of selected family members and confirmed by Sanger sequencing of all family members. Cochlear expression of Dmxl2 was investigated by reverse-transcription polymerase chain reaction (RT-PCR) and immunostaining of the organ of Corti from mice.
  
  
  
  The causative gene was mapped to a 9.68-Mb candidate region on chromosome 15q21.2 (maximum logarithm of the odds score = 4.03) that contained no previously described deafness genes. Whole-exome sequencing identified heterozygous c.7250G>A (p.Arg2417His) in DMXL2 as the only candidate pathogenic variant segregating the hearing loss. In mouse cochlea, expression of DMXL2 was restricted to the hair cells and the spiral ganglion neurons.
  
  
  
  Our data indicated that the p.Arg2417His variant in DMXL2 is associated with dominant, nonsyndromic hearing loss and suggested an important role of DMXL2 in inner ear function.Genet Med advance online publication 22 September 2016.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Dong-Ye
authors.initials: DY
authors.lastname: Chen
authors.affiliation: State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Xing-Feng
authors.identifier: 0000-0002-7518-5797
authors.initials: XF
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, People's Hospital of Kaihua, Kaihua, China.
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Lin
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Yong-Chuan
authors.initials: YC
authors.lastname: Chai
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: De-Hong
authors.identifier: 0000-0002-7949-3842
authors.initials: DH
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Chang-Ling
authors.initials: CL
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Xue-Ling
authors.identifier: 0000-0002-6310-0071
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Lian-Hua
authors.initials: LH
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Fu-Xin
authors.initials: FX
authors.lastname: Shi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Zhi-Wu
authors.initials: ZW
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D017668:Age of Onset; D000818:Animals; D002681:China / Q000208:ethnology; D003638:Deafness / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009925:Organ of Corti / Q000378:metabolism*; D010375:Pedigree; D020161:Physical Chromosome Mapping; D000073359:Exome Sequencing
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C452848:DMXL2 protein, human; C576980:DMXL2 protein, mouse; D009419:Nerve Tissue Proteins