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A Iannaccone, BM Yashar, ML Ciccarelli, EL Bingham, V Gasparri, A Baldi, MM Jablonski, R Ayyaggari, PA Sieving; Phenotype of X-Linked Juvenile Retinoschisis (XLRS) Associated With RS1 Missense Mutations . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1181.
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Purpose: To investigate the clinical and functional manifestations in males with XLRS from three families harboring distinct missense mutations of the RS1 gene. Methods: Genomic DNA was isolated from peripheral blood samples collected from the probands and screened for mutations in the RS1 gene. All patients were evaluated clinically and by ERG testing. Monochromatic light- and dark-adapted automated perimetry was performed in selected cases to measure cone- and rod-mediated thresholds. Results: Screening of the RS1 gene by sequencing of PCR-amplified DNA identified three previously reported missense mutations (G70S, W112C, R197C). All examined subjects had reduced visual acuity and electronegative maximal ERG responses, due to selective b-wave attenuation. The W112C mutation caused a remarkably mild phenotype, with a visual acuity of 20/30 in the better eye of the 52-year old proband and no macular or peripheral RS. ERG findings were asymmetric, with amplitude reduction and timing delay paralleling the extent of mid-peripheral patchy retinal metallic sheen. The phenotype caused by the R197C mutation was the most severe, with marked light aversion, visual acuity ≤20/100 by age 23, macrocystic macular and peripheral RS, and history of retinal detachment (RD). Rod ERGs were normal and cone ERGs were mildly subnormal. The timing of the cone ERGs increased sharply as a function of flash intensity. The G70S mutation yielded an intermediate phenotype, with moderate visual acuity reduction, microcystic macular and peripheral RS, and history of RD. Rod ERGs were mildly subnormal, while cone ERGs were normal. Perimetric loci showed greater rod (15-20 dB) than cone (5 dB or less) sensitivity losses in areas of macular RS. Bullous RS caused deep losses of both rod and cone sensitivity, with areas of rod sensitivity loss exceeding that of cones. Conclusion: The XLRS phenotypes associated with these mutations were variable in a non age-dependent manner and dysplayed interocular asymmetry. The severity of light aversion paralleled that of the macular RS changes, and was greater in patients with larger cone ERG reductions and delays. The extent of the peripheral metallic sheen correlated with the severity of ERG changes. Schitic regions showed greater rod than cone sensitivity losses. Further studies are needed to determine the level of intrafamilial consistency and prognostic value of these findings.
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