Identification of a Novel Copy Number Variation of EYA4 Causing Autosomal Dominant Non-syndromic Hearing Loss.
Journal
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
ISSN: 1537-4505
Titre abrégé: Otol Neurotol
Pays: United States
ID NLM: 100961504
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
pubmed:
17
4
2021
medline:
27
7
2021
entrez:
16
4
2021
Statut:
ppublish
Résumé
Eyes absent 4 (EYA4) is the causative gene of autosomal dominant non-syndromic hereditary hearing loss, DFNA10. We aimed to identify a copy number variation of EYA4 in a non-syndromic sensory neural hearing loss pedigree. A Japanese family showing late-onset and progressive hearing loss was evaluated. A pattern of autosomal dominant inheritance of hearing loss was recognized in the pedigree. No cardiac disease was observed in any of the individuals. Targeted exon sequencing was performed using massively parallel DNA sequencing (MPS) analysis. Scanning of the array comparative genomic hybridization (aCGH) was completed and the copy number variation (CNV) data from the aCGH analysis was confirmed by matching all CNV calls with MPS analysis. Breakpoint detection was performed by whole-genome sequencing and direct sequencing. Sequencing results were examined, and co-segregation analysis of hearing loss was completed. We identified a novel hemizygous indel that showed CNV in the EYA4 gene from the position 133,457,057 to 133,469,892 on chromosome 6 (build GRCh38/hg38) predicted as p.(Val124_Pro323del), and that was segregated with post-lingual and progressive autosomal dominant sensorineural hearing loss by aCGH analysis. Based on the theory of genotype-phenotype correlation with EYA4 mutations in terms of hearing loss and comorbid dilated cardiomyopathy, the region of amino acids 124 to 343 is hypothesized not to be the pathogenic region causing dilated cardiomyopathy. Additionally, the theory of genotype-phenotype correlation about the prevalence of dilated cardiomyopathy is thought to be rejected because of no correlation of deleted amino acid region with the prevalence of dilated cardiomyopathy. These results will help expand the research on both the coordination of cochlear transcriptional regulation and normal cardiac gene regulation via EYA4 transcripts and provide information on the genotype-phenotype correlations of DFNA10 hearing loss.
Identifiants
pubmed: 33859130
doi: 10.1097/MAO.0000000000003169
pii: 00129492-202108000-00016
doi:
Substances chimiques
EYA4 protein, human
0
Trans-Activators
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e866-e874Informations de copyright
Copyright © 2021, Otology & Neurotology, Inc.
Déclaration de conflit d'intérêts
The author discloses no conflicts of interest.
Références
Wayne S, Robertson NG, DeClau F, et al. Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Hum Mol Genet 2001; 10:195–200.
Verstreken M, Declau F, Schatteman I, et al. Audiometric analysis of a Belgian family linked to the DFNA10 locus. Am J Otol 2000; 21:675–681.
O’Neill ME, Marietta J, Nishimura D, et al. A gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6. Hum Mol Genet 1996; 5:853–856.
Borsani G, DeGrandi A, Ballabio A. EYA4, a novel vertebrate gene related to Drosophila eyes absent. Hum Mol Genet 1999; 8:11–23.
Bonini NM, Leiserson WM, Benzer S. The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. Cell 1993; 72:379–395.
Heanue TA, Reshef R, Davis RJ, et al. Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation. Genes Dev 1999; 13:3231–3243.
Tadjuidje E, Hegde RS. The Eyes Absent proteins in development and disease. Cell Mol Life Sci 2013; 70:1897–1913.
Schönberger J, Wang L, Shin JT, et al. Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nat Genet 2005; 37:418–422.
Schönberger J, Levy H, Grünig E, et al. Dilated cardiomyopathy and sensorineural hearing loss: a heritable syndrome that maps to 6q23-24. Circulation 2000; 101:1812–1818.
Makishima T, Madeo AC, Brewer CC, et al. Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain. Am J Med Genet part A 2007; 143A:1592–1598.
Usami SI, Nishio SY, Nagano M, et al. Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study. PLos ONE 2012; 7:e31276.
De Kok JB, Wiegerinck ET, Giesendorf BA, et al. Rapid genotyping of single nucleotide polymorphisms using novel minor groove binding DNA oligonucleotides (MGB probes). Hum Mutat 2002; 19:554–559.
Nishio SY, Moteki H, Usami SI. Simple and efficient germline copy number variant visualization method for the Ion AmpliSeq™ custom panel. Mol Genet Genomic Med 2018; doi: 10.1002/mgg3.399.
doi: 10.1002/mgg3.399
Moteki H, Azaiez H, Sloan-Heggen CM, et al. Detection and confirmation of deafness-causing copy number variations in the STRC gene by massively parallel sequencing and comparative genomic hybridization. Ann Otol Rhinol Laryngol 2016; 125:918–923.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17:405–424.
Shinagawa J, Moteki H, Nishio SY, et al. Prevalence and clinical features of hearing loss caused by EYA4 variants. Scientific Reports 2020; 10:3662.
Wang L, Sewell WF, Kim SD, et al. Eya4 regulation of Na+/K+-ATPase is required for sensory system development in zebrafish. Development 2008; 135:3425–3434.
Choi BY, Park G, Gim J, et al. Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss. PLoS One 2013; 8:e68692.
Pfister M, Toth T, Thiele H, et al. A 4-bp insertion in the eyahomologous region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10. Mol Med 2002; 8:607–611.
Hildebrand MS, Coman D, Yang T, et al. A novel splice site mutation in EYA4 causes DFNA10 hearing loss. Am J Med Gen part A 2007; 143A:1599–1604.
Baek JI, Oh SK, Kim DB, et al. Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families. Orphanet J Rare Dis 2012; 7:60.
Liu F, Hu J, Xia W, et al. Exome sequencing identifies a mutation in EYA4 as a novel cause of autosomal dominant non-syndromic hearing loss. PLoS One 2015; 10:e0126602.
Kim YR, Kim MA, Sagong B, et al. Evaluation of the contribution of the EYA4 and GRHL2 genes in Korean patients with autosomal dominant non-syndromic hearing loss and GRHL2 genes in Korean patients with autosomal dominant non-syndromic hearing loss. PLoS One 2015; 10:e0119443.
Miszalski-Jamka K, Jefferies JL, Mazur W, et al. Novel genetic triggers and genotype-phenotype correlations in patients with left ventricular noncompaction. Circ Cardiovasc Genet 2017; 10:e001763.
van Beelen E, Oonk AM, Leijendeckers JM, et al. Audiometric characteristics of a Dutch DFNA10 family with mid-frequency hearing impairment. Ear Hear 2016; 37:103–111.
Frykholm C, Klar J, Arnesson H, et al. Phenotypic variability in a seven-generation Swedish family segregating autosomal dominant hearing impairment due to a novel EYA4 frameshift mutation. Gene 2015; 563:10–16.
Huang A, Yuan Y, Liu Y, et al. A novel EYA4 mutation causing hearing loss in a Chinese DFNA family and genotype-phenotype review of EYA4 in deafness. J Transl Med 2015; 13:154.
Varga L, Danis D, Skopkova M, et al. Novel EYA4 variant in Slovak family with late onset autosomal dominant hearing loss: a case report. BMC Med Genet 2019; 20:84.
Choi HS, Kim AR, Kim SH, et al. Identification of a novel truncation mutation of EYA4 in moderate degree hearing loss by targeted exome sequencing. Eur Arch Otorhinolaryngol 2016; 273:1123–1129.
Iwasa YI, Nishio SY, Usami SI. Comprehensive genetic analysis of Japanese autosomal dominant sensorineural hearing loss patients. PLoS One 2016; 11:e0166781.
Hu S, Sun F, Zhang J, et al. Genetic etiology study of Ten Chinese Families with nonsyndromic hearing loss. Neural Plast 2018; 4920980.