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Brief Report
August 2016

Recessive Retinopathy Consequent on Mutant G-Protein β Subunit 3 (GNB3)

Author Affiliations
  • 1University College London Institute of Ophthalmology, London, England
  • 2Moorfields Eye Hospital, London, England
  • 3Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany
  • 4University College London Genetics Institute, London, England
JAMA Ophthalmol. 2016;134(8):924-927. doi:10.1001/jamaophthalmol.2016.1543

Importance  Mutations in phototransduction and retinal signaling genes are implicated in many retinopathies. To our knowledge, GNB3 encoding the G-protein β subunit 3 (Gβ3) has not previously been implicated in human disease.

Observations  In this brief report, whole-exome sequencing was conducted on a patient with distinct inherited retinal disease presenting in childhood, with a phenotype characterized by nystagmus, normal retinal examination, and mild disturbance of the central macula on detailed retinal imaging. This sequencing revealed a homozygous GNB3 nonsense mutation (c.124C>T; p.Arg42Ter). Whole-exome sequencing was conducted from April 2015 to July 2015.

Conclusions and Relevance  Expressed in cone photoreceptors and ON-bipolar cells, Gβ3 is essential in phototransduction and ON-bipolar cell signaling. Knockout of Gnb3 in mice results in dysfunction of cone photoreceptors and ON-bipolar cells and a naturally occurring chicken mutation leads to retinal degeneration. Identification of further affected patients may allow description of the phenotypic and genotypic spectrum of disease associated with GNB3 retinopathy.