Title

Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.

Document Type

Article

Publication Date

2001

Keywords

Amino-Acid-Sequence, Animal, Blotting-Northern, Blotting-Western, Cadherins, Cochlea, DNA-Mutational-Analysis, Deafness, Female, Fetus, Gene-Expression-Profiling, Human, In-Situ-Hybridization-Fluorescence, Linkage-(Genetics), Male, Mice, Molecular-Sequence-Data, Mutation, Pedigree, Polymorphism-Single-Stranded-Conformational, Protein-Precursors, Retina, Reverse-Transcriptase-Polymerase-Chain-Reaction, Sequence-Homology-Amino-Acid, SUPPORT-U-S-GOVT-P-H-S, Syndrome

JAX Source

Hum Mol Genet 2001 Aug 1; 10(16):1709-18.

Grant

HD07104/HD/NICHD, RO1DC02842/DC/NIDCD, RO1DC03420/DC/NIDCD

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.