title: Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population.
abstract: OBJECTIVE
  This study was designed to delineate genetic contributions, if any, to sporadic forms of mild to moderate sensorineural hearing loss (SNHL) not related to GJB2 mutations (DFNB1) in a pediatric population.
  
  
  METHODS
  We recruited 11 non-DFNB1 simplex cases of mild to moderate SNHL in children. We applied whole-exome sequencing to all 11 probands. We used a filtering strategy assuming that de novo variants of known autosomal dominant (AD) deafness genes, biallelic mutations in autosomal recessive (AR) genes, monoallelic mutations in X chromosome genes for males, and digenic inheritance could be associated. Candidate variants first were prioritized with allele frequency in public databases and confirmed by a phase or a segregation test in each family. Additional information from the literature or public databases was used to identify strong candidate variants.
  
  
  RESULTS
  Strong candidate variants were detected in 5 of 11 probands (45.4%). A diverse mode of inheritance implicated the sporadic occurrence of the phenotype. AR mutations in OTOGL and SERPINB6 and digenic inheritance involving two deafness genes, GPR98 and PDZ7, were detected. A de novo AD mutation also was detected in TECTA and MYH14. No syndromic feature was detected in individuals with GPR98/PDZ7 or MYH14 variants in our cohort at this moment.
  
  
  CONCLUSIONS
  Mild to moderate pediatric SNHL, even if sporadic, features a strong genetic etiology and can manifest via diverse modes of inheritance. In addition, a multidisciplinary approach should be used for a correct diagnosis.
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Nayoung K D
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, Korea.|Seoul ENT Clinic, Gimhae, Korea.
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Park
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.|Samsung Advanced Institute for Health Sciences and Technology, Seoul, Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Nam
authors.forename: Se Joon
authors.initials: SJ
authors.lastname: Woo
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Seung-Ha
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.|Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Seoul, Korea.
authors.forename: Woong-Yang
authors.identifier: http://orcid.org/0000-0003-4234-0380
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Byung Yoon
authors.initials: BY
authors.lastname: Choi
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000235:genetics*; D006320:Hearing Tests; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D040582:Inheritance Patterns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D012720:Severity of Illness Index
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26