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


METHODS
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
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.
University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
Gavin
G
Arno
University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
Graham E
GE
Holder
University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
Christina
C
Chakarova
Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
Susanne
S
Kohl
University College London Genetics Institute, London, England.
Nikolas
N
Pontikos
University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
Alessia
A
Fiorentino
University College London Genetics Institute, London, England.
Vincent
V
Plagnol
University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
Michael E
ME
Cheetham
University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
Alison J
AJ
Hardcastle
University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
Andrew R
AR
Webster
University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
Michel
M
Michaelides
D002648:Child; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005808:Genes, Recessive; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D010375:Pedigree; D012160:Retina / Q000000981:diagnostic imaging*; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D041623:Tomography, Optical Coherence
D018389:Codon, Nonsense; C000595803:GNB3 protein, human; D004247:DNA; D020962:Heterotrimeric GTP-Binding Proteins