Application of a New Genetic Deafness Microarray for Detecting Mutations in the Deaf in China

Wu, Hong; Jiang, Lu; Pan, Qian; Liu, Chang; He, Chufeng; Chen, Hongsheng; Liu, Xueming; Hu, Cong; Hu, Yuantai; Mei, Lingyun

doi:10.1371/journal.pone.0151909

Cited by 14 publications

(19 citation statements)

References 35 publications

(37 reference statements)

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“…The hearing of some patients may improve, while others' hearing loss may remain stable for a long time or even worsen. Among the very limited reports involving the follow-up characteristics of AN patients, the hearing outcomes in a long-term follow-up remain elusive [ 43 ]. Not surprisingly, we found, in the 50 AIFM1 -positive cases, that the low frequency spectra were mostly affected, especially in the 0.25-1 kHz range.…”

Section: Discussionmentioning

confidence: 99%

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

Wang

Dai

et al. 2020

Neural Plasticity

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To decipher the genotype-phenotype correlation of auditory neuropathy (AN) caused by AIFM1 variations, as well as the phenotype progression of these patients, exploring the potential molecular pathogenic mechanism of AN. A total of 36 families of individuals with AN (50 cases) with AIFM1 variations were recruited and identified by Sanger sequencing or next-generation sequencing; the participants included 30 patients from 16 reported families and 20 new cases. We found that AIFM1-positive cases accounted for 18.6% of late-onset AN cases. Of the 50 AN patients with AIFM1 variants, 45 were male and 5 were female. The hotspot variation of this gene was p.Leu344Phe, accounting for 36.1%. A total of 19 AIFM1 variants were reported in this study, including 7 novel ones. A follow-up study was performed on 30 previously reported AIFM1-positive subjects, 16 follow-up cases (53.3%) were included in this study, and follow-up periods were recorded from 1 to 23 years with average 9.75±9.89 years. There was no hearing threshold increase during the short-term follow-up period (1-10 years), but the low-frequency and high-frequency hearing thresholds showed a significant increase with the prolongation of follow-up time. The speech discrimination score progressed gradually and significantly along with the course of the disease and showed a more serious decline, which was disproportionately worse than the pure tone threshold. In addition to the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is also observed in AIFM1-related AN and affects females. In conclusion, we confirmed that AIFM1 is the primary related gene among late-onset AN cases, and the most common recurrent variant is p.Leu344Phe. Except for the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is another probability of AIFM1-related AN, with females affected. Phenotypical features of AIFM1-related AN suggested that auditory dyssynchrony progressively worsened over time.

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Section: Discussionmentioning

confidence: 99%

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

Wang

Dai

et al. 2020

Neural Plasticity

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“…It is reported that almost 80% of NSHL cases involve autosomal-recessive inheritance with high genetic heterogeneity (Angeli et al, 2012). The major symptom of autosomal-recessive NSHL (ARNSHL) is bilaterally symmetric, severe-to-profound, and prelingual sensorineural HL, which is known to be caused mainly by monogenic mutations (Wu et al, 2016; Deng et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Proband Whole-Exome Sequencing Identified Genes Responsible for Autosomal Recessive Non-Syndromic Hearing Loss in 33 Chinese Nuclear Families

et al. 2019

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Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous disease involving more than 70 pathogenic genes. However, most ARNSHL families have small-sized pedigrees with limited genetic information, rendering challenges for the molecular diagnosis of these patients. Therefore, we attempted to establish a strategy for identifying deleterious variants associated with ARNSHL by applying proband whole-exome sequencing (proband-WES). Aside from desiring to improve molecular diagnostic rates, we also aimed to search for novel deafness genes shared by patients with similar phenotype, making up for the deficiency of small ARNSHL families. In this study, 48.5% (16/33) families were detected the pathogenic variants in eight known deafness genes, including 10 novel variants identified in TMPRSS3 (MIM 605551), MYO15A (MIM 602666), TMC1 (MIM 606706), ADGRV1 (MIM 602851), and PTPRQ (MIM 603317). Apart from six novel variants with a truncating effect (nonsense, deletion, insertion, and splice-site), four novel missense variants were not found in 200 unrelated control population by using Sanger sequencing. It is important to note that none of novel genes were shared across different pedigrees, indicating that a larger sample size might be needed. Proband-WES is a cost-effective and precise way of identifying causative variants in nuclear families with ARNSHL. This economical strategy may be appropriated as a clinical application to provide molecular diagnostics, genetic counseling, and individualized health maintenance measures for patients with ARNSHL at hearing clinics.

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“…A recently developed genome-wide association approach to detect loci affecting PDS susceptibility used 597 genotyped sows with 62,163 single nucleotide polymorphisms (SNPs) [11]. We developed a microarray to detect 240 variants underlying syndromic and nonsyndromic sensorineural hearing loss, including 11 distinct variants in SLC26A4 [12]. However, all of these EVA genetic diagnosis strategies rely upon either full gene sequencing or test for common variants in only the SLC26A4 gene.…”

Section: Introductionmentioning

confidence: 99%

A New Genetic Diagnostic for Enlarged Vestibular Aqueduct Based on Next-Generation Sequencing

Wang

Liu³

et al. 2016

PLoS ONE

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Enlarged vestibular aqueduct (EVA) is one of the most common congenital inner ear malformations and accounts for 1–12% of sensorineural deafness in children and adolescents. Multiple genetic defects contribute to EVA; therefore, early molecular diagnosis is critical for EVA patients to ensure that the most effective treatment strategies are employed. This study explored a new genetic diagnosis method for EVA and applied it to clinic diagnoses of EVA patients. Using next-generation sequencing technology, we set up a multiple polymerase chain reaction enrichment system for target regions of EVA pathogenic genes (SLC26A4, FOXI1, and KCNJ10). Forty-six EVA samples were sequenced by this system. Variants were detected in 87.0% (40/46) of cases, including three novel variants (SLC26A4 c.923_929del, c.1002-8C>G, and FOXI1 c.519C>A). Biallelic potential pathogenic variants were detected in 27/46 patient samples, leading to a purported diagnostic rate of 59%. All results were verified by Sanger sequencing. Our target region capture system was validated to amplify and measure SLC26A4, FOXI1, and KCNJ10 in one reaction system. The result supplemented the mutation spectrum of EVA. Thus, this strategy is an economic, rapid, accurate, and reliable method with many useful applications in the clinical diagnosis of EVA patients.

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Application of a New Genetic Deafness Microarray for Detecting Mutations in the Deaf in China

Cited by 14 publications

References 35 publications

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

Proband Whole-Exome Sequencing Identified Genes Responsible for Autosomal Recessive Non-Syndromic Hearing Loss in 33 Chinese Nuclear Families

A New Genetic Diagnostic for Enlarged Vestibular Aqueduct Based on Next-Generation Sequencing

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