title: High prevalence of CDH23 mutations in patients with congenital high-frequency sporadic or recessively inherited hearing loss.
abstract: BACKGROUND
  Mutations in CDH23 are responsible for Usher syndrome 1D and recessive non-syndromic hearing loss. In this study, we revealed the prevalence of CDH23 mutations among patients with specific clinical characteristics.
  
  
  METHODS
  After excluding patients with GJB2 mutations and mitochondrial m.1555A > G and m.3243A > G mutations, subjects for CDH23 mutation analysis were selected according to the following criteria: 1) Sporadic or recessively inherited hearing loss 2) bilateral non-syndromic congenital hearing loss, 3) no cochlear malformation, 4) a poorer hearing level at high frequencies than at low frequencies, and 5) severe or profound hearing loss at higher frequencies.
  
  
  RESULTS
  Seventy-two subjects were selected from 621 consecutive probands who did not have environmental causes for their hearing loss. After direct sequencing, 13 of the 72 probands (18.1%) had homozygous or compound heterozygous CDH23 mutations. In total, we identified 16 CDH23 mutations, including five novel mutations. The 16 mutations included 12 missense, two frameshift, and two splice-site mutations.
  
  
  CONCLUSIONS
  These results revealed that CDH23 mutations are highly prevalent in patients with congenital high-frequency sporadic or recessively inherited hearing loss and that the mutation spectrum was diverse, indicating that patients with these clinical features merit genetic analysis.
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan. tari@mbf.ocn.ne.jp.|Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 160-8582, Japan. tari@mbf.ocn.ne.jp.
authors.forename: Kunio
authors.initials: K
authors.lastname: Mizutari
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan. mutaihideki@kankakuki.go.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Mutai
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan. nambakazunori@kankakuki.go.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Namba
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan. miyasama@lib.bekkoame.ne.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miyanaga
authors.affiliation: Division of Otorhinolaryngology, Chiba Children's Hospital, 579-1 Hetacho, Midori-ku, Chiba, Chiba, 266-0007, Japan. a.nkn@pref.chiba.lg.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakano
authors.affiliation: Division of Otorhinolaryngology, Chiba Children's Hospital, 579-1 Hetacho, Midori-ku, Chiba, Chiba, 266-0007, Japan. y.armt1@pref.chiba.lg.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Arimoto
authors.affiliation: Department of Otorhinolaryngology, National Mie Hospital, 357 Osato-Kubota, Tsu, Mie, 514-0125, Japan. masudas@mie-m.hosp.go.jp.
authors.forename: Sawako
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Division of Otolaryngology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. morimoto-n@ncchd.go.jp.
authors.forename: Noriko
authors.initials: N
authors.lastname: Morimoto
authors.affiliation: Department of Otorhinolaryngology, Hyogo Prefectural Kobe Children's Hospital, 1-1-1 Takakuradai, Suma-ku, Kobe, Hyogo, 654-0081, Japan. GED02037@nifty.com.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan. kaga@kankakuki.go.jp.
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Kaga
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan. matsunagatatsuo@kankakuki.go.jp.|Medical Genetics Center, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan. matsunagatatsuo@kankakuki.go.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsunaga
mesh_terms: D000293:Adolescent; D000328:Adult; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis; D005260:Female; D034381:Hearing Loss / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D055815:Young Adult
chemical_list: C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26