Early truncation of the N‐terminal variable region of <i>EYA4</i> gene causes dominant hearing loss without cardiac phenotype

Mi, Yanfang; Liu, Danhua; Zeng, Beiping; Tian, Yongan; Zhang, Hui; Chen, Bei; Zhang, Juanli; Xue, Hong; Tang, Wenxue; Zhao, Yue; Xu, Hongen

doi:10.1002/mgg3.1569

Cited by 8 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The precise molecular pathological mechanism by which EYA4 mutations cause hearing impairment has not been de ned but may be related to reduced gene dosage or reduced protein activity [15]. It has been shown that EYA4 gene-de cient mice develop hereditary otitis media, suggesting that EYA4 regulation is essential for the development and function of the middle ear cavity and Eustachian tube [16].…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel mutation of EYA4 in a Chinese family with delayed nonsyndromic hearing loss and analysis of molecular epidemiology of EYA4 mutations

Junfang,

Linyi,

Qiuchen

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: EYA4 is responsible for DFNA10 deafness. Because of its insidious onset and slow progression, hearing loss in ADSHL is usually difficult to detect early in clinical settings and the intervention is relatively backward. Genetic testing can help to detect hearing loss early and facilitate early intervention, effectively reducing the disability rate and improving the quality of life of patients. Methods: In this study, we report a Chinese family with delayed onset and progressive hearing loss that passed down for four generations. The whole-exome sequencing (WES) was performed on DNA samples from the proband. Candidate variants in the proband and his family members were confirmed by Sanger sequencing. In silico prediction tools and co-segregation analyses were used to determine the pathogenicity of identified variants. A literature review of known EYA4 mutations was performed, and the mutation frequency, distribution characteristics in different populations, and correlation between genotypes and phenotypes were analyzed. Results: We identified a novel EYA4 gene mutation, c.1745_1748del (p.Glu582ValfsTer6), in a Chinese family with nonsyndromic ADNSHL. This mutation was predicted to result in a frameshift and a stop codon after six additional amino acids and confirmed co-segregation with the phenotype of this family. To date, 52 pathogenic mutations in EYA4have been reported, and most of these mutations have been identified in Asian populations: 15 mutations in Japan, 10 in China, and four in Korea. In addition, the EYA4 mutation is not a common pathogenic gene of ADNSHL, and its audiological features are highly heterogeneous. Conclusions: A novel mutation in EYA4was identified in a Chinese family with delayed-onset deafness, further enriching the mutation spectrum of EYA4. The audiological features of EYA4mutations are highly heterogeneous and usually difficult to detect early in clinical settings. Our findings highlight the importance of genetic testing in patients with late-onset hearing loss.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of a novel mutation of EYA4 in a Chinese family with delayed nonsyndromic hearing loss and analysis of molecular epidemiology of EYA4 mutations

Junfang,

Linyi,

Qiuchen

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, the EYA4 variant reportedly causes dilated cardiomyopathy accompanying NSHL in a single large family. In this family, a 4846-bp genomic deletion that resulted in loss of the EYA domain (eyaHR) and part of the variable region (eyaVR) was detected [ 32 ]. A heterozygous deletion of 2747 bp represented a copy variant loss encompassing exon 15 to exon 17 [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel CNV at the EYA4 gene in a Chinese family with autosomal dominant nonsyndromic hearing loss

et al. 2022

View full text Add to dashboard Cite

Background Hereditary hearing loss is a heterogeneous class of disorders that exhibits various patterns of inheritance and involves many genes. Variants in the EYA4 gene in DFNA10 are known to lead to postlingual, progressive, autosomal dominant nonsyndromic hereditary hearing loss. Patients and methods We collected a four-generation Chinese family with autosomal-dominant nonsyndromic hearing loss (ADNSHL). We applied targeted next-generation sequencing (TNGS) in three patients of this pedigree and whole-genome sequencing (WGS) in the proband. The intrafamilial cosegregation of the variant and the deafness phenotype were confirmed by PCR, gap-PCR and Sanger sequencing. Results A novel CNV deletion at 6q23 in exons 8–11 of the EYA4 gene with a 10 bp insertion was identified by TNGS and WGS and segregated with the ADNSHL phenotypes. Conclusions Our results expanded the variant spectrum and genotype‒phenotype correlation of the EYA4 gene and autosomal dominant nonsyndromic hereditary hearing loss in Chinese Han individuals. WGS is an accurate and effective method for verifying the genomic features of CNVs.

show abstract

“…Bioinformatics analysis and variant interpretation were carried out as described previously [ 16 ]. Sequencing adapters and low-quality reads were trimmed from the raw reads using Trimmomatic [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Missense Variant of Endoplasmic Reticulum Region of WFS1 Gene Causes Autosomal Dominant Hearing Loss without Syndromic Phenotype

Sun

et al. 2021

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Objective. Genetic variants in the WFS1 gene can cause Wolfram syndrome (WS) or autosomal dominant nonsyndromic low-frequency hearing loss (HL). This study is aimed at investigating the molecular basis of HL in an affected Chinese family and the genotype-phenotype correlation of WFS1 variants. Methods. The clinical phenotype of the five-generation Chinese family was characterized using audiological examinations and pedigree analysis. Target exome sequencing of 129 known deafness genes and bioinformatics analysis were performed among six patients and four normal subjects to screen suspected pathogenic variants. We built a complete WFS1 protein model to assess the potential effects of the variant on protein structure. Results. A novel heterozygous pathogenic variant NM_006005.3 c.2020G>T (p.Gly674Trp) was identified in the WFS1 gene, located in the C-terminal domain of the wolframin protein. We further showed that HL-related WFS1 missense variants were mainly concentrated in the endoplasmic reticulum (ER) domain. In contrast, WS-related missense variants are randomly distributed throughout the protein. Conclusions. In this family, we identified a novel variant p.Gly674Trp of WFS1 as the primary pathogenic variant causing the low-frequency sensorineural HL, enriching the mutational spectrum of the WFS1 gene.

show abstract

Early truncation of the N‐terminal variable region of EYA4 gene causes dominant hearing loss without cardiac phenotype

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 8 publications

References 48 publications

Identification of a novel mutation of EYA4 in a Chinese family with delayed nonsyndromic hearing loss and analysis of molecular epidemiology of EYA4 mutations

Identification of a novel mutation of EYA4 in a Chinese family with delayed nonsyndromic hearing loss and analysis of molecular epidemiology of EYA4 mutations

Identification of a novel CNV at the EYA4 gene in a Chinese family with autosomal dominant nonsyndromic hearing loss

Missense Variant of Endoplasmic Reticulum Region of WFS1 Gene Causes Autosomal Dominant Hearing Loss without Syndromic Phenotype

Contact Info

Product

Resources

About