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

Ophthalmic Genet. 2021 Feb;42(1):62-70. doi: 10.1080/13816810.2020.1832533. Epub 2020 Oct 13.

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; electrophysiology; fundus autofluorescence; microperimetry; natural history; optical coherence tomography; rod-cone dystrophy.

Publication types

  • Case Reports
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Australia
  • Calcium-Binding Proteins / genetics*
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Retinitis Pigmentosa / etiology
  • Retinitis Pigmentosa / metabolism
  • Retinitis Pigmentosa / pathology*
  • Tumor Suppressor Proteins / genetics*
  • Visual Fields

Substances

  • Calcium-Binding Proteins
  • DMBT1 protein, human
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins