PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.
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.
Section of Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, USA.
Zubair M
ZM
Ahmed
Saima
S
Riazuddin
Jamil
J
Ahmad
Steve L
SL
Bernstein
Yan
Y
Guo
Muhammad F
MF
Sabar
Paul
P
Sieving
Sheikh
S
Riazuddin
Andrew J
AJ
Griffith
Thomas B
TB
Friedman
Inna A
IA
Belyantseva
Edward R
ER
Wilcox
D000368:Aged; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003051:Cochlea / Q000378:metabolism*; D003638:Deafness / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D005808:Genes, Recessive; D008040:Genetic Linkage; D000882:Haplorhini; D006801:Humans; D008126:Lod Score; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020125:Mutation, Missense; D010375:Pedigree; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000235:genetics
C418976:CDHR15 protein, mouse; C498835:CDHR15, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D011498:Protein Precursors