PCDH15 gene

Overview
Usher syndrome
Additional information
References

Overview

Gene (OMIM No.)	PCDH15 (#605514)
Function of gene/protein	Cell adhesion protein Component of the stereociliary links in the inner ear hair cell bundles Required for normal development and function of hair cell stereocilia
Clinical phenotype (OMIM phenotype no.)	Usher syndrome type 1F (#602083) Autosomal recessive hearing loss (#609533)
Inheritance	Autosomal recessive
Ocular features	Retinitis pigmentosa (Usher syndrome only)
Visual function	Usher syndrome Nyctalopia with pre-adolescent onset Peripheral visual field loss Loss of central and colour vision in later life
Systemic features	Congenital, bilateral, severe to profound sensorineural hearing loss Failed newborn hearing screen or hearing difficulties suspected in infancy Vestibular dysfunction affecting balance from birth
Key investigations	Newborn hearing screen – otoacoustic emission and automated auditory brainstem response Pure tone audiometry Electrophysiology Fundus autofluorescence (FAF): a ring of hyper-AF in the macula Optical coherence tomography (OCT): progressive loss of outer retinal structures which spares the fovea initially; cystoid macular oedema may be detected Kinetic perimetry
Molecular diagnosis	Next generation sequencing Targeted gene panels (retinal and deafness) Whole exome sequencing Whole genome sequencing Targeted exome sequencing
Management	Cochlear implantation within first two years of life Management of RP Management of Usher syndrome
Therapies under research	Nonsense suppression therapy (pre-clinical)
Further information	Medline Plus

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Additional information

PCDH15 mutations can cause both Usher syndrome type 1F^[4] or non-syndromic autosomal recessive hearing loss (DFNB23).^[5] There is evidence of a genotype–phenotype correlation; missense variants are primarily associated with non-syndromic deafness, whereas frameshift, nonsense and splice site mutations cause Usher type 1F.^[5,6]

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References

Rebibo-Sabbah A, Nudelman I, Ahmed ZM, Baasov T, Ben-Yosef T. In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome. Hum Genet. 2007;122(3-4):373-381
Nudelman I, Rebibo-Sabbah A, Cherniavsky M, et al. Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations. J Med Chem. 2009;52(9):2836-2845
Nudelman I, Glikin D, Smolkin B, Hainrichson M, Belakhov V, Baasov T. Repairing faulty genes by aminoglycosides: development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations. Bioorg Med Chem. 2010;18(11):3735-3746
Ahmed ZM, Riazuddin S, Bernstein SL, et al. Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. Am J Hum Genet. 2001;69(1):25-34
Ahmed ZM, Riazuddin S, Ahmad J, et al. PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23. Hum Mol Genet. 2003;12(24):3215-3223
Doucette L, Merner ND, Cooke S, et al. Profound, prelingual nonsyndromic deafness maps to chromosome 10q21 and is caused by a novel missense mutation in the Usher syndrome type IF gene PCDH15. Eur J Hum Genet. 2009;17(5):554-564

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Updated on November 30, 2020

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