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

We have determined the molecular basis for Usher syndrome type 1F (USH1F) i n two families segregating for this type of syndromic deafness. By fluoresc ence in situ hybridization, we placed the human homolog of the mouse protoc adherin Pcdh15 in the linkage interval defined by the USH1F locus. We deter mined 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 ex on 2 in the second. Consistent with the phenotypes observed in these famili es, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PC R and immunohistochemistry. This report shows that protocadherins are essen tial for maintenance of normal retinal and cochlear function.