Application of SNPscan in Genetic Screening for Common Hearing Loss Genes

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

doi:10.1371/journal.pone.0165650

PLoS ONE

2016

DOI: 10.1371/journal.pone.0165650

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Application of SNPscan in Genetic Screening for Common Hearing Loss Genes

Zixuan Gao

Yu Lu

Jia Ke

et al.

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 M… Show more

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Cited by 2 publications

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Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene

Tian

Liu

et al. 2021

Molec Gen & Gen Med

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Background The enlarged vestibular aqueduct (EVA) is the commonest malformation of inner ear accompanied by sensorineural hearing loss in children. Three genes SLC26A4, FOXI1, and KCNJ10 have been associated with EVA, among them SLC26A4 being the most common. Yet, hotspot mutation screening can only diagnose a small number of patients. Methods Thus, in this study, we designed a new molecular diagnosis panel for EVA based on multiplex PCR enrichment and next‐generation sequencing of the exon and flanking regions of SLC26A4. A total of 112 hearing loss families with EVA were enrolled and the pathogenicity of the rare variants detected was interpreted according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results Our results showed that 107/112 (95.54%) families carried SLC26A4 biallelic mutations, 4/112 (3.57%) carried monoallelic variants, and 1/112 (0.89%) had none variant, resulting in a diagnostic rate of 95.54%. A total of 49 different variants were detected in those patients and we classified 30 rare variants as pathogenic/likely pathogenic, of which 13 were not included in the Clinvar database. Conclusion Our diagnostic panel has an increased diagnostic yield with less cost, and the curated list of pathogenic variants in the SLC26A4 gene can be directly used to aid the genetic counseling to patients.

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Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene

Tian

Liu

et al. 2021

Molec Gen & Gen Med

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Exonic Deletions and Deep Intronic Variants of the SLC26A4 Gene Contribute to the Genetic Diagnosis of Unsolved Patients With Enlarged Vestibular Aqueduct

Tian,

Liu,

et al. 2024

Human Mutation

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Enlarged vestibular aqueduct (EVA) is a frequently occurring inner ear malformation that associates with sensorineural hearing loss (SNHL), with SLC26A4 being the responsible gene. Based on multiplex PCR enrichment and sequencing of the exonic and flanking regions of the SLC26A4 gene, we developed a panel specifically for EVA and found that up to 95% of EVA patients in our Chinese cohorts carried biallelic SLC26A4 pathogenic variants (M2). In this study, we tried to investigate the genetic etiology of 13 previously undiagnosed EVA patients with monoallelic (M1) or none (M0) SLC26A4 variant using a stepwise approach, including copy number variation (CNV) analysis of multiplex PCR enrichment and next‐generation sequencing data, single‐molecule real‐time (SMRT) sequencing of the whole SLC26A4 gene, whole exome sequencing (WES), and whole genome sequencing (WGS). CNV analysis revealed deletions in Exons 1–3, Exons 5–6, and Exons 9–10 of the SLC26A4 gene in seven patients, and SMRT sequencing identified the same heterozygous deep intronic variant (NM_000441.2:c.304+941C>T) in two patients, resulting in a final diagnosis in 9/13 patients. Notably, the variants of Exons 9–10 deletion and c.304+941C>T have not been reported previously. We further showed that the variant c.304+941C>T led to the exonization of partial AluSz6 element (126 bp) where the variant is located through sequencing of the mRNA extracted from the blood of a heterozygous variant carrier. In conclusion, our stepwise approach improved the diagnosis rate of EVA, expanded the mutational spectrum of the SLC26A4 gene, and highlighted the contribution of exonic deletions and deep intronic variants to EVA.

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Application of SNPscan in Genetic Screening for Common Hearing Loss Genes

Cited by 2 publications

References 20 publications

Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene

Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene

Exonic Deletions and Deep Intronic Variants of the SLC26A4 Gene Contribute to the Genetic Diagnosis of Unsolved Patients With Enlarged Vestibular Aqueduct

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