Progressive sector retinitis pigmentosa due to c.440G>T mutation in SAG in an Australian family

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.

KEYWORDS:

• S-antigen visual arrestin (SAG) gene
• autosomal dominant
• rod-cone dystrophy
• fundus autofluorescence
• optical coherence tomography
• microperimetry
• electrophysiology
• natural history

Acknowledgments

The AIRDR gratefully acknowledges the assistance of Ling Hoffman and Isabella Urwin of the Department of Medical Technology and Physics, Sir Charles Gairdner Hospital. We also acknowledge the support from Amanda Scurry and Jayme Glynn of Lions Eye Institute in organizing appointments for these patients.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by Australian National Health and Medical Research Council [GNT1054712, GNT1188694, MRF1142962]; McCusker Foundation; Australian National Health and Medical Research Council [GNT116360];Miocevich Retina Fellowship; Retina Australia; The sponsors or funding organizations had no role in the design or conduct of this research.