Application of SNPscan in Genetic Screening for Common Hearing Loss Genes.

Zixuan Gao,Lei Zhang,Hong Duan,Ping Hu,Jia Ke,Yu Lu,Jing Cheng,Huijun Yuan,Yu Song,Jie Wang,Tao Li,Furong Ma,Chiyu Xu,Obul Reddy Bandapalli

doi:10.1371/journal.pone.0165650

Abstract

The current study reports the successful application of a fast and efficient genetic screening system for common hearing loss (HL) genes based on SNPscan genotyping technology. Genetic analysis of 115 variants in common genes related to HL, GJB2, SLC26A4 and MT-RNR, was performed on 695 subjects with non-syndromic hearing loss (NSHL) from the Northern China. The results found that 38.7% (269/695) of cases carried bi-allelic pathogenic variants in GJB2 and SLC26A4 and 0.7% (5/695) of cases carried homoplasmic MT-RNR1 variants. The variant allele frequency of GJB2, SLC26A4 and MT-RNR1 was 19.8% (275/1390), 21.9% (304/1390), and 0.86% (6/695), respectively. This approach can explain ~40% of NSHL cases and thus is a useful tool for establishing primary molecular diagnosis of NSHL in clinical genetics.

Highlights

Hearing loss (HL) is one of the most common sensorineural disorders, affecting 1–2 neonates in every 1000 and the prevalence increases with age [1]
The current study reports the successful application of a fast and efficient genetic screening system for common hearing loss (HL) genes based on SNPscan genotyping technology
The results found that 38.7% (269/695) of cases carried bi-allelic pathogenic variants in GJB2 and SLC26A4 and 0.7% (5/695) of cases carried homoplasmic MTRNR1 variants

Summary

Introduction

Hearing loss (HL) is one of the most common sensorineural disorders, affecting 1–2 neonates in every 1000 and the prevalence increases with age [1]. 50% to 60% of childhood HL can be attributed to genetic defects[1]. Autosomal recessive (AR) NSHL is typically pre-lingual and is present in ~80% of HL cases. GJB2 is (OMIMÃ121011) the most common gene involved in ARNSHL. Pathogenic GJB2 variants account for up to 50% of all ARNSHL cases [2]. SLC26A4 (OMIMÃ605646), the second most frequent gene involved in ARNSHL and is present in 4–10% of NSHL cases among different populations [3,4,5]. A defect in the mitochondrial gene, MT-RNR1, is associated with extreme sensitivity to aminoglycoside ototoxicity and accounts for maternally inherited NSHL [6, 7]. Direct sequencing is the gold standard approach for genetic testing, it is expensive, time consuming and has low throughput. An SNPscan technique has been developed, using a patented SNP genotyping technology based on a double ligation reaction and multiplex fluorescence PCR, PLOS ONE | DOI:10.1371/journal.pone.0165650 October 28, 2016

Methods

Results

Conclusion