A Novel Homozygous Truncating GNAT1 Mutation Implicated in Retinal Degeneration

Overview

Journal Br J Ophthalmol

Specialty Ophthalmology

Date 2015 Oct 17

PMID 26472407

Citations 19

Authors

Matthew Carrigan

Emma Duignan

Pete Humphries

Arpad Palfi

Paul F Kenna

G Jane Farrar

Affiliations

Soon will be listed here.

Abstract

Background: The GNAT1 gene encodes the α subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated in retinitis pigmentosa.

Methods: A panel of 182 retinopathy-associated genes was sequenced to locate disease-causing mutations in patients with inherited retinopathies.

Results: Sequencing revealed a novel homozygous truncating mutation in the GNAT1 gene in a patient with significant pigmentary disturbance and constriction of visual fields, a presentation consistent with retinitis pigmentosa. This is the first report of a patient homozygous for a complete loss-of-function GNAT1 mutation. The clinical data from this patient provide definitive evidence of retinitis pigmentosa with late onset in addition to the lifelong night-blindness that would be expected from a lack of transducin function.

Conclusion: These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, late-onset retinal degeneration in human beings rather than just stationary night-blindness as reported previously, with notable similarities to the phenotype of the Gnat1 knockout mouse.

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