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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BMC Medical Genetics 1/2017

A novel pore-region mutation, c.887G > A (p.G296D) in KCNQ4, causing hearing loss in a Chinese family with autosomal dominant non-syndromic deafness 2

Zeitschrift:
BMC Medical Genetics > Ausgabe 1/2017
Autoren:
Bangqing Huang, Yanping Liu, Xue Gao, Jincao Xu, Pu Dai, Qingwen Zhu, Yongyi Yuan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12881-017-0396-5) contains supplementary material, which is available to authorized users.

Abstract

Background

Hereditary non-syndromic hearing loss is the most common inherited sensory defect in humans. The KCNQ4 channel belongs to a family of potassium ion channels that play crucial roles in physiology and disease. Mutations in KCNQ4 underlie deafness non-syndromic autosomal dominant 2, a subtype of autosomal dominant, progressive, high-frequency hearing loss.

Methods

A six-generation Chinese family from Hebei Province with autosomal dominantly inherited, sensorineural, postlingual, progressive hearing loss was enrolled in this study. Mutation screening of 129 genes associated with hearing loss was performed in five family members by next-generation sequencing (NGS). We also carried out variant analysis on DNA from 531 Chinese individuals with normal hearing as controls.

Results

This family exhibits postlingual, progressive, symmetrical, bilateral, non-syndromic sensorineural hearing loss. NGS, bioinformatic analysis, and Sanger sequencing confirmed the co-segregation of a novel mutation [c.887G > A (p.G296D)] in KCNQ4 with the disease phenotype in this family. This mutation leads to a glycine-to-aspartic acid substitution at position 296 in the pore region of the KCNQ4 channel. This mutation affects a highly conserved glutamic acid. NGS is a highly efficient tool for identifying gene mutations causing heritable disease.

Conclusions

Progressive hearing loss is common in individuals with KCNQ4 mutations. NGS together with Sanger sequencing confirmed that the five affected members of this Chinese family inherited a missense mutation, c.887G > A (p.G296D), in exon 6 of KCNQ4. Our results increase the number of identified KCNQ4 mutations.
Zusatzmaterial
Additional file 1: Table S1. Potential deafness causing variants found by NGS. (DOCX 14 kb)
12881_2017_396_MOESM1_ESM.docx
Additional file 2: Table S2. Depth and coverage information of DFNA2 locus in NGS. (DOCX 14 kb)
12881_2017_396_MOESM2_ESM.docx
Literatur
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