title: Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.
abstract: We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.
authors.affiliation: Department of Pediatrics, Rainbow Babies and Children's Hospital, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Alagramam
authors.forename: H
authors.initials: H
authors.lastname: Yuan
authors.forename: M H
authors.initials: MH
authors.lastname: Kuehn
authors.forename: C L
authors.initials: CL
authors.lastname: Murcia
authors.forename: S
authors.initials: S
authors.lastname: Wayne
authors.forename: C R
authors.initials: CR
authors.lastname: Srisailpathy
authors.forename: R B
authors.initials: RB
authors.lastname: Lowry
authors.forename: R
authors.initials: R
authors.lastname: Knaus
authors.forename: L
authors.initials: L
authors.lastname: Van Laer
authors.forename: F P
authors.initials: FP
authors.lastname: Bernier
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.forename: C C
authors.initials: CC
authors.lastname: Morton
authors.forename: R F
authors.initials: RF
authors.lastname: Mullins
authors.forename: A
authors.initials: A
authors.lastname: Ramesh
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
authors.forename: G S
authors.initials: GS
authors.lastname: Hageman
authors.forename: R P
authors.initials: RP
authors.lastname: Woychik
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: G S
authors.initials: GS
authors.lastname: Hagemen
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000032:analysis / Q000235:genetics*; D003051:Cochlea / Q000737:chemistry; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D005260:Female; D005333:Fetus; D020869:Gene Expression Profiling; D008040:Genetic Linkage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics*; D012160:Retina / Q000737:chemistry / Q000196:embryology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: C418976:CDHR15 protein, mouse; C498835:CDHR15, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D011498:Protein Precursors