PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23

• Published in: Human molecular genetics Vol. 12; no. 24; pp. 3215 - 3223
• Main Authors: Ahmed, Zubair M., Riazuddin, Saima, Ahmad, Jamil, Bernstein, Steve L., Guo, Yan, Sabar, Muhammad F., Sieving, Paul, Riazuddin, Sheikh, Griffith, Andrew J., Friedman, Thomas B., Belyantseva, Inna A., Wilcox, Edward R.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.12.2003; Oxford Publishing Limited (England)
• Subjects: Aged; Alleles; Animals; Base Sequence; Biological and medical sciences; Cadherins - genetics; Cadherins - metabolism; Classical genetics, quantitative genetics, hybrids; Cochlea - metabolism; Deafness - genetics; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Epithelium - metabolism; Fundamental and applied biological sciences. Psychology; Genes, Recessive; Genetic Linkage; Genetics of eukaryotes. Biological and molecular evolution; Haplorhini; Human; Humans; Lod Score; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mutation, Missense; Non tumoral diseases; Otorhinolaryngology. Stomatology; PCDH15 gene; Pedigree; Protein Precursors - genetics; Protein Precursors - metabolism; protocadherin 15; Retina - metabolism; Retinitis Pigmentosa - genetics; Usher syndrome; Human; Retinopathy; Nutrition disorder; Auditory disorder; Epithelium; Gene expression; Genetic disease; Hearing loss; Eye; Eye disease; Usher syndrome; Ear; ENT disease; Mutation; Molecular biology
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddg358

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.