Genetic Epidemiology and Clinical Features of Hereditary Hearing Impairment in the Taiwanese Population.

Chen Chen,Cheng Cheng,Erdenechuluun Erdenechuluun,Hsu Hsu,Lee Lee,Lin Lin,Liu Liu,Tsai Tsai,Wu Wu

doi:10.3390/genes10100772

Abstract

Hereditary hearing impairment (HHI) is a common but heterogeneous clinical entity caused by mutations in a plethora of deafness genes. Research over the past few decades has shown that the genetic epidemiology of HHI varies significantly across populations. In this study, we used different genetic examination strategies to address the genetic causes of HHI in a large Taiwanese cohort composed of >5000 hearing-impaired families. We also analyzed the clinical features associated with specific genetic mutations. Our results demonstrated that next-generation sequencing-based examination strategies could achieve genetic diagnosis in approximately half of the families. Common deafness-associated genes in the Taiwanese patients assessed, in the order of prevalence, included GJB2, SLC26A4, OTOF, MYO15A, and MTRNR1, which were similar to those found in other populations. However, the Taiwanese patients had some unique mutations in these genes. These findings may have important clinical implications for refining molecular diagnostics, facilitating genetic counseling, and enabling precision medicine for the management of HHI.

Highlights

Hearing impairment is the most common inherited sensory defect
Sanger sequencing of the three common deafness genes
There is solid evidence that the use of the next-generation sequencing (NGS) technique can significantly increase the diagnostic yield of genetic examination for Hereditary hearing impairment (HHI) and facilitate the genetic counseling for the affected families

Summary

Introduction

Hearing impairment is the most common inherited sensory defect. It is estimated that permanent sensorineural hearing impairment (SNHI) occurs in approximately 1.9 out of 1000 live births [1], and including late-onset SNHI, the disorder may affect 2% of school-age children [2,3]. About one-half to two-thirds of SNHI cases in children are attributed to genetic causes and are classified as hereditary hearing impairment (HHI) [4]. More than 100 genes have been identified as causally related to HHI (http://hereditaryhearingloss.org). Because different genetic mutations represent different pathogeneses and are related to different clinical outcomes, identifying etiology is crucial in the assessment and management of childhood SNHI. Over the past two decades, research has revealed that the genetic epidemiology of HHI varies across populations.

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Results

Discussion

Conclusion