A dominant variant in DMXL2 is linked to nonsyndromic hearing loss

Genet Med. 2017 May;19(5):553-558. doi: 10.1038/gim.2016.142. Epub 2016 Sep 22.


Purpose: To explore the genetic etiology of deafness in a dominant family with late-onset, progressive, nonsyndromic hearing loss.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Age of Onset
  • Animals
  • China / ethnology
  • Deafness / genetics*
  • Deafness / metabolism
  • Exome Sequencing
  • Female
  • Genetic Association Studies
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mice
  • Mutation, Missense*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Organ of Corti / metabolism*
  • Pedigree
  • Physical Chromosome Mapping


  • Adaptor Proteins, Signal Transducing
  • DMXL2 protein, human
  • DMXL2 protein, mouse
  • Nerve Tissue Proteins

Supplementary concepts

  • Nonsyndromic Deafness