Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH.

Xiaodong Gu,Mingliang Tang,Liping Zhao,Wenling Su,Luo Guo,Huawei Li

doi:10.1155/2016/5310192

Abstract

DFNA9 is a late-onset, progressive, autosomal dominantly inherited sensorineural hearing loss with vestibular dysfunction, which is caused by mutations in the COCH (coagulation factor C homology) gene. In this study, we investigated a Chinese family segregating autosomal dominant nonsyndromic sensorineural hearing loss. We identified a missense mutation c.T275A p.V92D in the LCCL domain of COCH cosegregating with the disease and absent in 100 normal hearing controls. This mutation leads to substitution of the hydrophobic valine to an acidic amino acid aspartic acid. Our data enriched the mutation spectrum of DFNA9 and implied the importance for mutation screening of COCH in age related hearing loss with vestibular dysfunctions.

Highlights

As the most common sensory impairment, hearing loss (HL) affects one of every 500 newborn infants, and its prevalence rises to 2.7 per 1000 children before the age of 5 and 3.5 per 1000 during adolescence [1, 2]
Mutations in the COCH gene are responsible for the lateonset, progressive ADNSHL with incomplete penetrance of vestibular malfunction known as DFNA9 [5]
Seven individuals in family G405 were diagnosed with sensorineural hearing loss by otologic and audiometric analysis (Figure 1(a))

Summary

Introduction

As the most common sensory impairment, hearing loss (HL) affects one of every 500 newborn infants, and its prevalence rises to 2.7 per 1000 children before the age of 5 and 3.5 per 1000 during adolescence [1, 2]. HL is a genetically and clinically heterozygous disorder and can be classified according to pattern of inheritance (autosomal dominant, autosomal recessive, or X-linked recessive, and mitochondrial inheritance), the absence (nonsyndromic) or presence (syndromic) of other clinical features, and age at onset (prelingual or postlingual) [3]. Most of the mutations in the autosomal dominant loci cause postlingual hearing impairments [4]. Mutations in the COCH gene are responsible for the lateonset, progressive ADNSHL with incomplete penetrance of vestibular malfunction known as DFNA9 [5]. The COCH gene encodes a 550-aa extracellular protein cochlin that is the most highly expressed protein in the human and mouse inner ear [6]. The cochlin amino acid sequence contains an Nterminal signal peptide, an LCCL domain highly homologous to factor C, a serine proteinase involved in immune response

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