Exome sequencing identifies POU4F3 as the causative gene for a large Chinese family with non-syndromic hearing loss

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 mut...

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Bibliographic Details
Published in:Journal of human genetics 2017-02, Vol.62 (2), p.317-320
Main Authors: Cai, Xin Zhang, Li, Ying, Xia, Lu, Peng, Yu, He, Chu Feng, Jiang, Lu, Feng, Yong, Xia, Kun, Liu, Xue Zhong, Mei, Ling Yun, Hu, Zheng Mao
Format: Article
Language:English
Subjects:
Asian Continental Ancestry Group - genetics
Base Sequence
Deafness
Exome - genetics
Frameshift mutation
Frameshift Mutation - genetics
Genomes
Hearing loss
Hearing Loss, Sensorineural - genetics
Hearing Loss, Sensorineural - pathology
Homeodomain Proteins - genetics
Humans
Mutation
Pedigree
Sequence Analysis, DNA
Transcription Factor Brn-3C - genetics
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Summary: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.
ISSN:1434-5161
1435-232X
DOI:10.1038/jhg.2016.102