Progressive sector retinitis pigmentosa due to c.440G>T mutation in SAG in an Australian family. (2nd January 2021)

• Record Type: Journal Article
• Authors: Pappalardo, Juanita; Heath Jeffery, Rachael C.; Thompson, Jennifer A.; Charng, Jason; Chelva, Enid S.; Constable, Ian J.; McLaren, Terri L.; Lamey, Tina M.; De Roach, John N.; Chen, Fred K.
• Is Part Of: Ophthalmic genetics. Volume 42:Number 1(2021)
• Page Start: 62
• Page End: 70
• Publication Date: 2021-01-02
• Subjects: S-antigen visual arrestin (SAG) gene -- autosomal dominant -- rod-cone dystrophy -- fundus autofluorescence -- optical coherence tomography -- microperimetry -- electrophysiology -- natural history; Eye -- Diseases -- Genetic aspects -- Periodicals; Eye Diseases -- genetics -- Periodicals; Eye Diseases -- in infancy & childhood -- Periodicals; 617.7
• DOI: 10.1080/13816810.2020.1832533
• Languages: English
• ISSNs: 1381-6810

Abstract

ABSTRACT: Background: Heterozygous c.440 G > T mutation in the S-antigen visual arrestin (SAG) gene has been described as a cause of autosomal dominant retinitis pigmentosa (adRP) in a series of patients of Hispanic origin. This study presents the early and late clinical features and disease progression rates in an Australian family with SAG adRP. Materials and methods: An observational case series of four family members with adRP. They were examined clinically, with multi-modal retinal imaging and electroretinography (ERG) to ascertain phenotype. Disease progression rate was measured using optical coherence tomography (OCT) and fundus autofluorescence (FAF). A retinal dystrophy panel was used for the proband and cascade testing with targeted Sanger sequencing was conducted in other available family members. Results: The proband presented at 36 years of age with profoundly reduced full-field ERG responses despite a sector RP phenotype. This progressed to a classic RP pattern over several decades leaving a small residual island of central visual field. The horizontal span of the residual outer nuclear layer and the area of hyperautofluorescent ring contracted at a rate of 8–11% and 9–14% per year, respectively. DNA sequencing confirmed the segregation of SAG c.440 G > T mutation with disease. Conclusion: SAG adRP presents with a reduced full-field ERG response consistent with a rod-cone dystrophy in mid-life despite a sector RP phenotype. Centripetal progression of the disease into the macula can be tracked by OCT and FAF imaging.