title: Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS.
abstract: Genetic factors, the most common etiology in severe to profound hearing loss, are one of the key determinants of Cochlear Implantation (CI) and Electric Acoustic Stimulation (EAS) outcomes. Satisfactory auditory performance after receiving a CI/EAS in patients with certain deafness gene mutations indicates that genetic testing would be helpful in predicting CI/EAS outcomes and deciding treatment choices. However, because of the extreme genetic heterogeneity of deafness, clinical application of genetic information still entails difficulties. Target exon sequencing using massively parallel DNA sequencing is a new powerful strategy to discover rare causative genes in Mendelian disorders such as deafness. We used massive sequencing of the exons of 58 target candidate genes to analyze 8 (4 early-onset, 4 late-onset) Japanese CI/EAS patients, who did not have mutations in commonly found genes including GJB2, SLC26A4, or mitochondrial 1555A>G or 3243A>G mutations. We successfully identified four rare causative mutations in the MYO15A, TECTA, TMPRSS3, and ACTG1 genes in four patients who showed relatively good auditory performance with CI including EAS, suggesting that genetic testing may be able to predict the performance after implantation.
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Miyagawa
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Nishio
authors.forename: Takuo
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Fukushima
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Usami
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D019929:Cochlear Implantation; D000072259:Connexin 26; D017630:Connexins; D003638:Deafness / Q000235:genetics*; D016326:Extracellular Matrix Proteins; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation; D009218:Myosins; D009363:Neoplasm Proteins; D017422:Sequence Analysis, DNA / Q000379:methods*; D012697:Serine Endopeptidases; D055815:Young Adult
chemical_list: D017630:Connexins; D016326:Extracellular Matrix Proteins; C000607042:GJB2 protein, human; D058851:GPI-Linked Proteins; C485245:MYO15A protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C491350:TECTA protein, human; D000072259:Connexin 26; D012697:Serine Endopeptidases; C409042:TMPRSS3 protein, human; D009218:Myosins