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

Importance

Mutations in phototransduction and retinal signaling genes are implicated in many retinopathies. To our knowledge,GNB3encoding 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 homozygousGNB3nonsense 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 ofGnb3in 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 withGNB3 retinopathy.