Abstract
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.
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Acknowledgements
We greatly thank the pedigree members for agreeing to participate in this study. We also appreciate the help and advice of our colleagues. This study was supported by the National Basic Research Program of China (also called 973 Program) (2012CB517902; 2014CB541702) and the National Nature Science Foundation of China (81300833; 31301023).
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Cai, X., Li, Y., Xia, L. et al. Exome sequencing identifies POU4F3 as the causative gene for a large Chinese family with non-syndromic hearing loss. J Hum Genet 62, 317–320 (2017). https://doi.org/10.1038/jhg.2016.102
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DOI: https://doi.org/10.1038/jhg.2016.102
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