title: De novo large genomic deletions involving POU3F4 in incomplete partition type III inner ear anomaly in East Asian populations and implications for genetic counseling.
abstract: OBJECTIVE
  The aim of this study was to understand the prevalence and molecular genetic etiology of incomplete partition type III (IP type III) anomaly in Koreans. We also attempted to verify the prevalence of genomic deletions in the DFNX2 locus and to look for association between inheritance patterns and mutation type in East Asian IP type III subjects.
  
  
  METHODS
  Retrospective case review.
  
  
  METHODS
  Tertiary referral center.
  
  
  METHODS
  Subjects with IP type III anomaly and their biological mothers.
  
  
  METHODS
  Sanger sequencing, array-comparative genomic hybridization (aCGH), and PCR were performed. We also analyzed the type and inheritance of the causative genetic abnormality in East Asian DFNX2 patients.
  
  
  METHODS
  Mutation type and occurrence.
  
  
  RESULTS
  We identified IP type III in 10 (4.8%) of 206 patients with an inner ear abnormality. We confirmed an etiologic homogeneity, DFNX2, of the IP type III in this Korean population. Two (20%) of the 10 DFNX2 carried a large genomic deletion affecting POU3F4, as proved by aCGH. PCR confirmed that the 2 deletions occurred de novo. Genetic alteration occurred de novo in 29.4% (5/17) of all reported Korean IP type III cases. From this study and literature review, we observed a striking difference of de novo occurrence rate (75% versus 12.5%, p = 0.032) between large genomic deletions and point mutations in East Asian population.
  
  
  CONCLUSIONS
  Our data suggest that different POU3F4 mutations might show different recurrence rate in siblings of the IP type III families, especially in East Asian population. Genetic counseling should be provided accordingly.
authors.affiliation: *Department of Otorhinolaryngology-Head and Neck Surgery, Chungnam National University Hospital, Daejeon; †Laboratory of Molecular and Genomic Medicine, Department of Biomedical Sciences, ‡Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul; §Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital; ∥Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul; ¶Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon; #Translational Genomics Laboratory, Samsung Institute, Samsung Medical Center, Seoul, Republic of Korea; and**Department of Cell and System Biology, University of Toronto, Toronto, Canada.
authors.forename: Jin Woong
authors.initials: JW
authors.lastname: Choi
authors.forename: ByungJoo
authors.initials: B
authors.lastname: Min
authors.forename: AhReum
authors.initials: A
authors.lastname: Kim
authors.forename: Ja-Won
authors.initials: JW
authors.lastname: Koo
authors.forename: Chong-Sun
authors.initials: CS
authors.lastname: Kim
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Juyong
authors.initials: J
authors.lastname: Chung
authors.forename: Veronica
authors.initials: V
authors.lastname: Kim
authors.forename: Yoon-Jong
authors.initials: YJ
authors.lastname: Ryu
authors.forename: Shin Hye
authors.initials: SH
authors.lastname: Kim
authors.forename: Sun-O
authors.initials: SO
authors.lastname: Chang
authors.forename: Seung-Ha
authors.initials: SH
authors.lastname: Oh
authors.forename: Byung Yoon
authors.initials: BY
authors.lastname: Choi
mesh_terms: D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D007758:Ear, Inner / Q000002:abnormalities*; D005260:Female; D005817:Genetic Counseling; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009035:Mothers; D009154:Mutation; D050809:POU Domain Factors / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D056910:Republic of Korea; D012189:Retrospective Studies; D017384:Sequence Deletion
chemical_list: D050809:POU Domain Factors; C091774:POU3F4 protein, human