Human Molecular Genetics Advance Access published online on October 21, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg358
© 2003 by Oxford University Press
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1 Section on Human Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD; National Center of Excellence in Molecular Biology, Punjab University, Lahore, Pakistan
* To whom correspondence should be addressed. E-mail: wilcoxe{at}nidcd.nih.gov.
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 nonsyndromic recessive hearing loss (DFNB23) is caused by missense mutations of PCDH15. This suggests a genotype-phenotype correlation in which hypomorphic alleles cause nonsyndromic 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.
Article
PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23
2 Section on Human Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD
3 National Center of Excellence in Molecular Biology, Punjab University, Lahore, Pakistan
4 Department of Ophthalmology, University of Maryland School of Medicine, Baltimore, MD
5 National Eye Institute, National Institutes of Health, Bethesda, MD
6 Section on Gene Structure and Function, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD; Hearing Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD
7 Section on Human Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD; 5 Research Court, 2A-19, Rockville, MD 20850, USA
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