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A.P. Booth, D. Trump, N.D. George; A Manifesting Female Heterozygote in X-linked Retinoschisis: Clinical and Genetic Study . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1484.
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Purpose: Familial retinoschisis is an X-linked condition. Affected males usually present at school age with difficulty in reading. It is characterised by foveal schisis and ectopia, peripheral retinoschisis, and a reduction of b-wave on ERG. There have been no previous reports of female carriers manifesting clinical or electrodiagnostic features of the disease. The purpose of this study was to perform a clinical and genetic examination of a three-generation family with X-linked retinoschisis. One affected family member was a 5 year old girl. Methods: Family members underwent a full ophthalmic examination including electrodiagnostic testing. DNA sequencing of the RS1 gene was performed. Results: The proband, a 42 year old male, and his 36 year old brother showed typical clinical features of X-linked retinoschisis. Significantly, the proband's 5 year old daughter also had bilateral peripheral retinoschisis and probable early foveal schisis. ERG testing was abnormal in all three affected individuals. In addition, the proband's maternal uncle was believed to have X-linked retinoschisis. Mutation testing demonstrated that the proband, his brother and daughter all had a G to A missense mutation at nucleotide 305 in exon 4 of the RS1 gene. This results in the substitution of arginine by glycine at codon 102. The mutation has previously been described in other families with X-linked retinoschisis and has been shown to prevent the secretion of the protein retinoschisin. The girl was heterozygous for the mutation. No other alteration from the normal sequence was detected in any of the six exons of the RS1 gene. Conclusions: This is the first description of a female, heterozygous for an RS1 mutation, manifesting typical clinical features of X-linked retinoschisis. The most likely explanation is that the girl has skewed X-inactivation in her retinal tissues.
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