title: Identification and Clinical Implications of Novel MYO15A Mutations in a Non-consanguineous Korean Family by Targeted Exome Sequencing.
abstract: Mutations of MYO15A are generally known to cause severe to profound hearing loss throughout all frequencies. Here, we found two novel MYO15A mutations, c.3871C>T (p.L1291F) and c.5835T>G (p.Y1945X) in an affected individual carrying congenital profound sensorineural hearing loss (SNHL) through targeted resequencing of 134 known deafness genes. The variant, p.L1291F and p.Y1945X, resided in the myosin motor and IQ2 domains, respectively. The p.L1291F variant was predicted to affect the structure of the actin-binding site from three-dimensional protein modeling, thereby interfering with the correct interaction between actin and myosin. From the literature analysis, mutations in the N-terminal domain were more frequently associated with residual hearing at low frequencies than mutations in the other regions of this gene. Therefore we suggest a hypothetical genotype-phenotype correlation whereby MYO15A mutations that affect domains other than the N-terminal domain, lead to profound SNHL throughout all frequencies and mutations that affect the N-terminal domain, result in residual hearing at low frequencies. This genotype-phenotype correlation suggests that preservation of residual hearing during auditory rehabilitation like cochlear implantation should be intended for those who carry mutations in the N-terminal domain and that individuals with mutations elsewhere in MYO15A require early cochlear implantation to timely initiate speech development.
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul national University College of Medicine, Seoul 110-744, Korea.
authors.forename: Mun Young
authors.initials: MY
authors.lastname: Chang
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul national University College of Medicine, Seoul 110-744, Korea.
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Korea.
authors.forename: Nayoung K D
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Korea.|Samsung Advanced Institute for Health Sciences and Technology, Seoul 135-710, Korea.
authors.forename: Chung
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Kyoung Yeul
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Jeon
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam 463-707, Korea.
authors.forename: Ja-Won
authors.initials: JW
authors.lastname: Koo
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul national University College of Medicine, Seoul 110-744, Korea.
authors.forename: Seung Ha
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Korea.|Samsung Advanced Institute for Health Sciences and Technology, Seoul 135-710, Korea.|Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Dongsup
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam 463-707, Korea.
authors.forename: Byung Yoon
authors.initials: BY
authors.lastname: Choi
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D019929:Cochlear Implantation; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics* / Q000601:surgery; D059472:Exome; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009218:Myosins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D056910:Republic of Korea; D017423:Sequence Analysis, RNA
chemical_list: C485245:MYO15A protein, human; D009218:Myosins
keywords: MYO15A; cochlear implantation; mutation; nonsyndromic sensorineural hearing loss (NSHL)