title: Discovery of CDH23 as a Significant Contributor to Progressive Postlingual Sensorineural Hearing Loss in Koreans.
abstract: CDH23 mutations have mostly been associated with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic or nonsyndromic SNHL (DFNB12). Herein, we demonstrate the contribution of CDH23 mutations to postlingual nonsyndromic SNHL (NS-SNHL). We screened 32 Korean adult probands with postlingual NS-SNHL sporadically or in autosomal recessive fashion using targeted panel or whole exome sequencing. We identified four (12.5%, 4/32) potential postlingual DFNB12 families that segregated the recessive CDH23 variants, qualifying for our criteria along with rapidly progressive SNHL. Three of the four families carried one definite pathogenic CDH23 variant previously known as the prelingual DFNB12 variant in a trans configuration with rare CDH23 variants. To determine the contribution of rare CDH23 variants to the postlingual NS-SNHL, we checked the minor allele frequency (MAF) of CDH23 variants detected from our postlingual NS-SNHL cohort and prelingual NS-SNHL cohort, among the 2040 normal control chromosomes. The allele frequency of these CDH23 variants in our postlingual cohort was 12.5%, which was significantly higher than that of the 2040 control chromosomes (5.53%), confirming the contribution of these rare CDH23 variants to postlingual NS-SNHL. Furthermore, MAF of rare CDH23 variants from the postlingual NS-SNHL group was significantly higher than that from the prelingual NS-SNHL group. This study demonstrates an important contribution of CDH23 mutations to poslingual NS-SNHL and shows that the phenotypic spectrum of DFNB12 can be broadened even into the presbycusis, depending on the pathogenic potential of variants. We also propose that pathogenic potential of CDH23 variants and the clinical fate of DFNB12 may be predicted by MAF.
authors: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors: Bong Jik
authors: http://orcid.org/0000-0002-6384-2171
authors: BJ
authors: Kim
authors: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors: Ah Reum
authors: AR
authors: Kim
authors: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon, Korea.
authors: Chung
authors: C
authors: Lee
authors: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors: So Young
authors: SY
authors: Kim
authors: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors: Nayoung K D
authors: NK
authors: Kim
authors: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors: Mun Young
authors: MY
authors: Chang
authors: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors: Jihye
authors: J
authors: Rhee
authors: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Korea.
authors: Mi-Hyun
authors: MH
authors: Park
authors: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Korea.
authors: Soo Kyung
authors: SK
authors: Koo
authors: Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Min Young
authors: MY
authors: Kim
authors: Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Jin Hee
authors: JH
authors: Han
authors: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors: Seung-Ha
authors: SH
authors: Oh
authors: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.|Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon, Korea.
authors: Woong-Yang
authors: WY
authors: Park
authors: Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Byung Yoon
authors: BY
authors: Choi
mesh_terms: D000328:Adult; D000368:Aged; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D057089:Pathology, Molecular; D056910:Republic of Korea; D055815:Young Adult
chemical_list: C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins