Human Molecular Genetics Advance Access originally published online on October 21, 2003
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Human Molecular Genetics, 2003, Vol. 12, No. 24 3215-3223
DOI: 10.1093/hmg/ddg358
© 2003 Oxford University Press
PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23
1Section on Human Genetics, 2Section on Gene Structure and Function, Laboratory of Molecular Genetics, and 3Hearing Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, USA, 4National Center of Excellence in Molecular Biology, Punjab University, Lahore, Pakistan, 5Department of Ophthalmology, University of Maryland School of Medicine, Baltimore, MD, USA and 6National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Received June 27, 2003; Accepted October 17, 2003
Recessive splice site and nonsense mutations of PCDH15, encoding protocadherin 15, are known to cause deafness and retinitis pigmentosa in Usher syndrome type 1F (USH1F). Here we report that non-syndromic recessive hearing loss (DFNB23) is caused by missense mutations of PCDH15. This suggests a genotype–phenotype correlation in which hypomorphic alleles cause non-syndromic hearing loss, while more severe mutations of this gene result in USH1F. We localized protocadherin 15 to inner ear hair cell stereocilia, and to retinal photoreceptors by immunocytochemistry. Our results further strengthen the importance of protocadherin 15 in the morphogenesis and cohesion of stereocilia bundles and retinal photoreceptor cell maintenance or function.
* To whom correspondence should be addressed at: 5 Research Court, 2A-19, Rockville, MD 20850, USA. Tel: +1 3014024162; Fax: +1 3014808019; Email: wilcoxe{at}nidcd.nih.gov
PCDH15 isoform B reported in this manuscript has been deposited in NCBI GenBank and the accession number is AY388963.
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