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.
Ahmed
Zubair M
ZM
Section of Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, USA.
Riazuddin
Saima
S
Ahmad
Jamil
J
Bernstein
Steve L
SL
Guo
Yan
Y
Sabar
Muhammad F
MF
Sieving
Paul
P
Riazuddin
Sheikh
S
Griffith
Andrew J
AJ
Friedman
Thomas B
TB
Belyantseva
Inna A
IA
Wilcox
Edward R
ER
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