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

A dominant variant in DMXL2 is linked to nonsyndromic hearing loss.

Chen DY1,2,3, Liu XF4, Lin XJ5, Zhang D6, Chai YC1,2,3, Yu DH1,2,3, Sun CL1,2,3, Wang XL1,2,3, Zhu WD1,2,3, Chen Y1,2,3, Sun LH1,2,3, Wang XW1,2,3, Shi FX2,3, Huang ZW1,2,3, Yang T1,2,3, Wu H1,2,3.

Author information

1
Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
2
Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
3
Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
4
State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
5
Department of Otolaryngology, People's Hospital of Kaihua, Kaihua, China.
6
Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Abstract

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.

PMID:
27657680
DOI:
10.1038/gim.2016.142
[Indexed for MEDLINE]

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