WHRN gene

Overview

Gene (OMIM no.)
Function of gene/protein
  • Scaffolding protein
  • Localises to the ankle links in the stereocilia of the developing inner ear hair cells
  • Required for correct post-natal development of stereocilia hair cells
  • Localises to the periciliary membrane complex at the photoreceptor connecting cilium
Clinical phenotype (with OMIM phenotype no.)
Inheritance
  • Autosomal recessive
Ocular features
Visual function
  • Nyctalopia starting around adolescence or later
  • Peripheral visual field loss
  • Loss of central and colour vision in later life
Systemic features Usher syndrome
  • Congenital bilateral sensorineural hearing loss; mild to moderate in low frequencies, and severe to profound in high frequencies
  • Failed newborn hearing screen or hearing difficulties suspected in infancy
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

WHRN mutations are associated with Usher syndrome type 2D or non-syndromic deafness (DFNB31). The associated phenotypes are thought to be dependent on the mutation location within the two predominantly expressed variants (long and short). N-terminal mutations that affect the long isoform are found in Usher patients,3,4 whereas mutations in the C-terminal region manifest as DFNB31.5,6

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References

  1. Zou J, Luo L, Shen Z, et al. Whirlin Replacement Restores the Formation of the USH2 Protein Complex in Whirlin Knockout Photoreceptors. Invest Ophthalmol Vis Sci. 2011;52(5):2343-2351.
  2. Isgrig K, Shteamer JW, Belyantseva IA, et al. Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome. Mol Ther. 2017;25(3):780-791.
  3. Ebermann I, Scholl HPN, Issa PC, et al. A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing loss. Hum Genet. 2007;121(2):203-211.
  4. Audo I, Bujakowska K, Mohand-Said S, et al. A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family. Mol Vis. 2011;17(178):1598-1606.
  5. Mburu P, Mustapha M, Varela A, et al. Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31. Nat Genet. 2003;34(4):421-428.
  6. Tlili A, Charfedine I, Lahmar I, et al. Identification of a novel frameshift mutation in the DFNB31/WHRN gene in a Tunisian consanguineous family with hereditary non-syndromic recessive hearing loss. Hum Mutat. 2005;25(5):503-503.

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Updated on August 18, 2023
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