CDH23 gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: Cadherin related 23
  • Cell adhesion protein
  • Component of the stereociliary links in the inner ear hair cell bundles
  • Required for the 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
  • None at present
Further information

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Additional information

CDH23 mutations can cause both Usher syndrome type 1D[1] or non-syndromic autosomal recessive hearing loss (DFNB12).[2] There is evidence of a genotype–phenotype correlation; missense variants are primarily associated with non-syndromic deafness or more subtle RP symptoms, whereas frameshift, nonsense and splice site mutations cause Usher type 1D.[2-4] However, missense mutations in CDH23 can also cause milder or ‘atypical’ Usher type 1 and genotype-phenotype correlations are not always predictable.[3]

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References

  1.  Bolz H, von Brederlow B, Ramirez A, et al. Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D. Nat Genet. 2001;27(1):108-112
  2.  Bork JM, Peters LM, Riazuddin S, et al. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Am J Hum Genet. 2001;68(1):26-37
  3.  Astuto LM, Bork JM, Weston MD, et al. CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness. Am J Hum Genet. 2002;71(2):262-275
  4.  Schultz JM, Bhatti R, Madeo AC, et al. Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes. J Med Genet. 2011;48(11):767-775

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Updated on November 30, 2020
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