PCDH15 gene

Overview

Gene (OMIM No.)
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.)
Inheritance
  • Autosomal recessive
Ocular features
Visual functionUsher 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 diagnosisNext generation sequencing
  • Targeted gene panels (retinal and deafness)
  • Whole exome sequencing
  • Whole genome sequencing
  • Targeted exome sequencing
Management
Therapies under research
Further information

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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

  1.  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
  2.  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
  3.  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
  4.  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
  5.  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
  6.  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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