Abstract
BackgroundHereditary hearing loss is a heterogeneous class of disorders showing various patterns of inheritance and involving many genes. Mutations in the EYA4 gene are responsible for postlingual, progressive, autosomal dominant hearing loss at the DFNA10 locus.MethodsWe report on a Chinese family with sensorineural, progressive hearing loss. Next-generation sequencing (NGS) was conducted using DNA samples from this family. A candidate mutation was confirmed by Sanger sequencing. A detailed genotype and phenotype analysis of EYA4 in deafness is provided.ResultsNGS revealed an insertion mutation c.544_545insA in exon 8 of EYA4 in all affected family members. This insertion created a frameshift resulting in a stop codon at position 221 (p.F221X). The p.F221X frameshift mutation cosegregated with hearing loss in the family. Audiograms of affected family members are flat or sloping, differing from the characteristic “cookie bite” audiogram and the mutation is localized in a different region of the eyaHR in EYA4.ConclusionsWe identified a novel frameshift mutation in the EYA4 gene. Our results enrich the mutational spectrum of EYA4 and highlight the complexity of the DFNA10 genotypes and phenotypes. Using NGS techniques to establish a database of common mutations in patients with hearing loss and further data accumulation will contribute to the early diagnosis and development of fundamental therapies for hereditary hearing loss.
Highlights
Hearing loss is one of the most common perception disorders and a highly heterogeneous sensory disorder
We examined the genetic basis of ADSHNL in a Chinese family by next-generation sequencing (NGS) and identified a novel mutation, p.F221X, in exon 8 of the Eyes absent 4” (EYA4) gene
The clinical history and audiological assessments of the eight affected members revealed a form of postlingual, bilateral, symmetrical, progressive, sensorineural hearing loss that affected both genders (Table 1)
Summary
Hearing loss is one of the most common perception disorders and a highly heterogeneous sensory disorder. Nonsyndromic hearing loss has both recessive and dominant modes of inheritance. It is estimated that 80% of the genetic forms of hearing loss are autosomal recessive and the remaining 20% are autosomal dominant [1]. Autosomal dominant non-syndromic hearing loss (ADNSHL) is characterized by heterogeneous genetic and clinical features. The capacity to simultaneously screen thousands of target genes makes this technique an especially powerful tool for detecting pathogenic mutations that cause heterogeneous disorders such as hereditary hearing loss [2]. Hereditary hearing loss is a heterogeneous class of disorders showing various patterns of inheritance and involving many genes. Mutations in the EYA4 gene are responsible for postlingual, progressive, autosomal dominant hearing loss at the DFNA10 locus
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
