Xiaohui Wu1,2, Xingqiang Gao2, Peng Han3, Yulin Zhou4. 1. a Xiamen Neonatal Hearing Screening and Diagnostic Center , Xiamen Maternity and Child Health Care Hospital , Siming District , Xiamen , China. 2. b Department of Otolaryngology-Head and Neck Surgery , Children's Hospital of Fudan University; Xiamen Branch; Xiamen Children's Hospital , Huli District, Xiamen , China. 3. c BGI, BGI-Shenzhen, Beishan Industrial Zone, Yantian District , Shenzhen , China. 4. d Xiamen Neonatal Disease Screening Center, Xiamen Maternity and Child Health Care Hospital , Xiamen , China.
Abstract
BACKGROUND: Due to extreme genetic heterogeneity, targeted next-generation sequencing (NGS) can be an efficient tool for rapid genetic diagnosis of hereditary non-syndromic hearing loss (NSHL). AIMS/ OBJECTIVES: This study was aiming to identify causative variants in NSHL patients from the Minnan region through targeted NGS. MATERIAL AND METHODS: Genomic DNA samples from 90 NSHL subjects were extracted and subjected to SureSelect target enrichment system to capture the entire coding exons and flanking intronic regions of gene GJB2, SLC26A4, and MT-RNR1. The captured DNA was then sequenced by Illumina HiSeq2500. The sequence data was processed and quality-checked using Burrows-Wheeler Alignment, Picard, and GATK, and annotated by SnpEff, SIFT, and GERP++. RESULTS: Twenty-six candidate variants in GJB2, SLC26A4, and MT-RNR1 were detected in 57 of 90 NSHL patients. GJB2 c.109G > A was the most frequent variant, followed by GJB2 c.608T > C and c.235delC. Genetic diagnosis was available for 22 NSHL patients, including 19 patients associated with autosomal recessive NSHL, one patients with autosomal dominant NSHL, and two individuals with mitochondrial disorders. CONCLUSIONS AND SIGNIFICANCE: Our targeted NGS analysis added supports for the application of NGS in routine diagnosis and provided an overview of genetic variants with allele frequencies in the deaf population from the Minnan region.
BACKGROUND: Due to extreme genetic heterogeneity, targeted next-generation sequencing (NGS) can be an efficient tool for rapid genetic diagnosis of hereditary non-syndromic hearing loss (NSHL). AIMS/ OBJECTIVES: This study was aiming to identify causative variants in NSHL patients from the Minnan region through targeted NGS. MATERIAL AND METHODS: Genomic DNA samples from 90 NSHL subjects were extracted and subjected to SureSelect target enrichment system to capture the entire coding exons and flanking intronic regions of gene GJB2, SLC26A4, and MT-RNR1. The captured DNA was then sequenced by Illumina HiSeq2500. The sequence data was processed and quality-checked using Burrows-Wheeler Alignment, Picard, and GATK, and annotated by SnpEff, SIFT, and GERP++. RESULTS: Twenty-six candidate variants in GJB2, SLC26A4, and MT-RNR1 were detected in 57 of 90 NSHL patients. GJB2 c.109G > A was the most frequent variant, followed by GJB2 c.608T > C and c.235delC. Genetic diagnosis was available for 22 NSHL patients, including 19 patients associated with autosomal recessive NSHL, one patients with autosomal dominant NSHL, and two individuals with mitochondrial disorders. CONCLUSIONS AND SIGNIFICANCE: Our targeted NGS analysis added supports for the application of NGS in routine diagnosis and provided an overview of genetic variants with allele frequencies in the deaf population from the Minnan region.
Authors: Samuel M Adadey; Kevin K Esoh; Osbourne Quaye; Geoffrey K Amedofu; Gordon A Awandare; Ambroise Wonkam Journal: Exp Biol Med (Maywood) Date: 2020-06-11
Authors: Samuel M Adadey; Noluthando Manyisa; Khuthala Mnika; Carmen de Kock; Victoria Nembaware; Osbourne Quaye; Geoffrey K Amedofu; Gordon A Awandare; Ambroise Wonkam Journal: Front Genet Date: 2019-09-18 Impact factor: 4.599