Identification of Main Genetic Causes Responsible for Non-Syndromic Hearing Loss in a Peruvian Population.

Figueroa-Ildefonso Figueroa-Ildefonso,Cornejo-Olivas Cornejo-Olivas,Rajabli Rajabli,Neyra Neyra,Inca-Martinez Inca-Martinez,Tekin Tekin,Villanueva Villanueva,Badillo-Carrillo Badillo-Carrillo,Sineni Sineni,Bademci Bademci

doi:10.3390/genes10080581

Abstract

Hearing loss (HL) is a common sensory disorder affecting over 5% of the global population. The etiology underlying HL includes congenital and acquired causes; genetic factors are the main cause in over 50% of congenital cases. Pathogenic variants in the GJB2 gene are a major cause of congenital non-syndromic hearing loss (NSHL), while their distribution is highly heterogeneous in different populations. To the best of our knowledge, there is no data regarding the genetic etiologies of HL in Peru. In this study, we screened 133 Peruvian families with NSHL living in Lima. We sequenced both exons of the GJB2 gene for all probands. Seven probands with familial NSHL that remained negative for GJB2 variants underwent whole genome sequencing (WGS). We identified biallelic pathogenic variants in GJB2 in 43 probands; seven were heterozygous for only one allele. The c.427C>T variant was the most common pathogenic variant followed by the c.35delG variant. WGS revealed three novel variants in MYO15A in two probands, one of them was predicted to affect splicing and the others produce a premature stop codon. The Peruvian population showed a complex profile for genetic variants in the GJB2 gene, this particular profile might be a consequence of the admixture history in Peru.

Highlights

Hearing loss (HL) is a common sensory disorder affecting over 5% of the global population [1].The etiology underlying HL includes congenital and acquired causes; genetic factors are causative in over 50% of congenital cases [2]
non-syndromic hearing loss (NSHL) were obtained from the biorepository of the Neurogenetics Research Center (NRC) at the Instituto Nacional de Ciencias Neurológicas (INCN), from Lima, Peru, collected for a previous study
The second proband was heterozygous for two variants: c.843C>A, which is a nonsense variant in exon 2, and c.8798delT, which produces a frameshift in the open reading frame of exon 50 (Table S5). These genetic variants have not been reported in the public databases gnomAD or 1000 genomes project. This is the first study where a Peruvian population with NSHL was screened for genetic variants in the GJB2 gene

Summary

Introduction

Hearing loss (HL) is a common sensory disorder affecting over 5% of the global population [1]. The etiology underlying HL includes congenital and acquired causes; genetic factors are causative in over 50% of congenital cases [2]. DNA variants in over 100 genes have been reported to cause non-syndromic hearing loss (NSHL) [4], and their distribution is highly heterogeneous in different populations [5]. Pathogenic variants in the GJB2 gene (NM_004004.6) are considered to be the major cause of congenital NSHL across populations [6]. The GJB2 gene has two exons; the second exon codes for the gap junction beta-2 (or Cx26) protein, involved in the maintenance of a high endocochlear potential [7]

Methods

Results

Conclusion