Novel EYA4 variant in Slovak family with late onset autosomal dominant hearing loss: a case report

BMC Medical Genetics

Daniel Danis¹  Martina Skopkova¹  Ivica Masindova¹  Daniela Gasperikova¹  Lucia Demesova²  Milan Profant²  Lukas Varga³  Zuzana Slobodova³ 

[1] 0000 0001 2180 9405, grid.419303.c, Diabgene Laboratory, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia;0000000109409708, grid.7634.6, Department of Otorhinolaryngology – Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University, Bratislava, Slovakia;0000000109409708, grid.7634.6, Department of Otorhinolaryngology – Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University, Bratislava, Slovakia;0000 0001 2180 9405, grid.419303.c, Diabgene Laboratory, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia;

关键词: Sensorineural deafness;    Postlingual;    Next-generation sequencing;    Autosomal dominant;   

DOI  :  10.1186/s12881-019-0806-y

来源: publisher

【 摘 要 】

BackgroundProgressive bilateral sensorineural deafness in postlingual period may be linked to many different etiologies including genetic factors. Identification of the exact deafness cause may, therefore, be quite challenging. Here we present a family with late-onset hearing loss as an autosomal dominant trait caused by a novel EYA4 mutation.Case presentationForty-four years old female proband clinically investigated for progressive hearing loss and occasional dizziness with positive family history for deafness was subject to molecular-genetic testing. Patient’s DNA sample was analyzed by whole exome sequencing. We identified a novel missense variant c.804G > C located at the last base pair of exon 10 in EYA4. Candidate variant was confirmed by Sanger sequencing in the proband and her family members. In silico prediction tools and co-segregation analysis were used to indicate pathogenicity of the identified variant. To confirm our hypothesis, we performed minigene assay to demonstrate if the transcript of exon 10 in EYA4 is present. We provide evidence that this mutation in vitro compromises donor site functionality and causes exon 10 skipping and frameshift that most likely results in nonsense-mediated mRNA decay. The onset of moderate to severe hearing loss in the family ranged from 10 to 40 years. The normal cardiac phenotype was confirmed by ECG and echocardiography.ConclusionsWe identified a novel EYA4 mutation associated with adult-onset autosomal dominant sensorineural hearing loss. This report extends the knowledge of spectrum of EYA4 mutations and demonstrates the pathogenicity of a variant affecting specific position in the gene. A comprehensive review of known EYA4 mutations is also given and their impact on cardiac phenotype is discussed. Our findings highlight the importance of genetic testing and complex clinical assessment in patients with familial progressive hearing loss.

【 授权许可】

CC BY