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David G Birch, Kaylie Webb-Jones, Martin Klein, Rui Chen, Lori S Sullivan, Sara J Bowne, Stephen P Daiger; SAG (S-antigen visual arrestin-1) mutations cause autosomal dominant retinitis pigmentosa (adRP) without the Oguchi disease phenotype. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3234.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in SAG are known to cause recessive Oguchi disease with congenial stationary night blindness and fundus pallor. However, a dominant acting mutation in SAG, p.Cys147Phe, is the cause of autosomal dominant retinitis pigmentosa in Hispanic families from the Southwest United States (Sullivan et al., ARVO, 2017). We present clinical findings in affected individuals with the SAG p.Cys147Phe mutation and compare to previously reported findings from patients with Oguchi disease.
Probands from seven families diagnosed with adRP were referred to the RFSW for clinical evaluation and collection of blood samples for genetic analysis. Six additional affected relatives and three unaffected individuals were also recruited for participation as pedigrees were expanded through patient interviews. Both retrospective and prospective clinical data included best-corrected visual acuity (EVA), visual fields (Humphrey and/or Octopus), ISCEV standard full-field ERGs (Espion), dark-adapted thresholds (Goldmann-Weekers) and SD-OCT (Heidelberg Spectralis).
SAG mutations were found in 13 patients ranging in age from 26 to 66 (mean age = 48 yrs). Patients under <45 yrs retained > 20/25 vision and, with one exception, retained at least 20/40 vision into their 60s. Rod ERGs were non-detectable in all but one patient tested at age 26, who retained a 4.0 microV response. Cone responses were reduced by 85% at age 45 and by 95% by age 60, consistent with the degree of field constriction. All patients showed elevations in final dark-adapted visual thresholds. Unlike in patients with Oguchi disease, extended (3 hrs) dark adaptation did not lead to a further gain in sensitivity. None of the patients with SAG mutations showed the Mizuo-Nakamura phenomenon characteristic of Oguchi disease associated with recessive SAG mutations. The fundus appearance was distinctive, however, with patients showing multiple hyperreflective spots, which appeared on OCT to be distributed through all retinal layers.
SAG mutations cause a distinctive form of adRP. Unlike patients with recessive SAG mutations, the patients with adRP show none of the characteristics of Oguchi disease.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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