title: Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.
abstract: Genes causing nonsyndromic autosomal recessive deafness (DFNB12) and deafness associated with retinitis pigmentosa and vestibular dysfunction (USH1D) were previously mapped to overlapping regions of chromosome 10q21-q22. Seven highly consanguineous families segregating nonsyndromic autosomal recessive deafness were analyzed to refine the DFNB12 locus. In a single family, a critical region was defined between D10S1694 and D10S1737, approximately 0.55 cM apart. Eighteen candidate genes in the region were sequenced. Mutations in a novel cadherin-like gene, CDH23, were found both in families with DFNB12 and in families with USH1D. Six missense mutations were found in five families with DFNB12, and two nonsense and two frameshift mutations were found in four families with USH1D. A northern blot analysis of CDH23 showed a 9.5-kb transcript expressed primarily in the retina. CDH23 is also expressed in the cochlea, as is demonstrated by polymerase chain reaction amplification from cochlear cDNA.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Bork
authors.forename: L M
authors.initials: LM
authors.lastname: Peters
authors.forename: S
authors.initials: S
authors.lastname: Riazuddin
authors.forename: S L
authors.initials: SL
authors.lastname: Bernstein
authors.forename: Z M
authors.initials: ZM
authors.lastname: Ahmed
authors.forename: S L
authors.initials: SL
authors.lastname: Ness
authors.forename: R
authors.initials: R
authors.lastname: Polomeno
authors.forename: A
authors.initials: A
authors.lastname: Ramesh
authors.forename: M
authors.initials: M
authors.lastname: Schloss
authors.forename: C R
authors.initials: CR
authors.lastname: Srisailpathy
authors.forename: S
authors.initials: S
authors.lastname: Wayne
authors.forename: S
authors.initials: S
authors.lastname: Bellman
authors.forename: D
authors.initials: D
authors.lastname: Desmukh
authors.forename: Z
authors.initials: Z
authors.lastname: Ahmed
authors.forename: S N
authors.initials: SN
authors.lastname: Khan
authors.forename: V M
authors.initials: VM
authors.lastname: Kaloustian
authors.forename: X C
authors.initials: XC
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Lalwani
authors.forename: S
authors.initials: S
authors.lastname: Riazuddin
authors.forename: M
authors.initials: M
authors.lastname: Bitner-Glindzicz
authors.forename: W E
authors.initials: WE
authors.lastname: Nance
authors.forename: X Z
authors.initials: XZ
authors.lastname: Liu
authors.forename: G
authors.initials: G
authors.lastname: Wistow
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: A J
authors.initials: AJ
authors.lastname: Griffith
authors.forename: E R
authors.initials: ER
authors.lastname: Wilcox
authors.forename: T B
authors.initials: TB
authors.lastname: Friedman
authors.forename: R J
authors.initials: RJ
authors.lastname: Morell
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D002874:Chromosome Mapping; D003241:Consanguinity; D004252:DNA Mutational Analysis; D017931:DNA Primers; D003638:Deafness / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008126:Lod Score; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics*; D013577:Syndrome
chemical_list: C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D017931:DNA Primers; D012333:RNA, Messenger