A Missense Mutation in POU4F3 Causes Midfrequency Hearing Loss in a Chinese ADNSHL Family.

Mei-Guang Zhang,Xue Gao,Dan Bai,Pu Dai,Wei-Qian Wang,Sha-Sha Huang,Yu Su,Jia Li,Guo-Jian Wang,Xi Lin,Yong-Yi Yuan,Jin-Cao Xu,Dong-Yang Kang

doi:10.1155/2018/5370802

Abstract

Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the POU class 4 transcription factor 3 (POU4F3) are known to cause autosomal dominant nonsyndromic hearing loss linked to the loci of DFNA15. In this study, we describe a pathogenic missense mutation in POU4F3 in a four-generation Chinese family (6126) with midfrequency, progressive, and postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 129 known deafness genes, next-generation sequencing, and bioinformatic analysis, we identified POU4F3 c.602T>C (p.Leu201Pro) as the disease-causing variant. This variant cosegregated with hearing loss in other family members but was not detected in 580 normal controls or the ExAC database and could be classified as a “pathogenic variant” according to the American College of Medical Genetics and Genomics guidelines. We conclude that POU4F3 c.602T>C (p.Leu201Pro) is related to midfrequency hearing loss in this family. Routine examination of POU4F3 is necessary for the genetic diagnosis of midfrequency hearing loss.

Highlights

Hearing loss is a common sensory defect in humans
Audiograms show that lowfrequency and high-frequency hearing were normal in the beginning, their hearing would deteriorate at all frequencies
We describe the clinical and genetic characteristics of a Chinese family with postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL) caused by POU class 4 transcription factor 3 (POU4F3) c. 602 T>C

Summary

Introduction

Hearing loss is a common sensory defect in humans. Nonsyndromic hereditary forms, in which hearing loss is the only clinical sign, are known to be genetically heterogeneous. More than 30 genes responsible for autosomal dominant nonsyndromic hearing loss (ADNSHL) have been identified (Hereditary Hearing Loss homepage, http://hereditaryhearingloss.org). Most patients with ADNSHL show large variations in age of onset and degrees of variety. According to the affected frequency, the phenotypes are divided into lowfrequency, midfrequency, high-frequency, and all-frequency hearing loss. Midfrequency hearing loss (i.e., a U-shape audiogram) is a rare form of hearing loss, and six associated genes have been reported to date: EYA4, TECTA, COL11A2, CCDC50, POU4F3, and SLC44A4 [1–6]. In clinical molecular diagnosis, the hearing loss phenotype in a patient can aid the selection of a limited number of genes for mutational analysis

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Conclusion