Genotypic and phenotypic spectrum of X-linked retinoschisis in Australia

Background: X-linked retinoschisis (XLRS), an X-linked recessive inherited degenerative retinopathy, is characterized by splitting in the nerve fibre layer and is caused by alterations in the RSI gene. The aim of the present study was to review both the phenotypic features of XLRS and the mutation spectrum of the RSI gene in an Australian cohort. Methods: Patients were recruited from ophthalmic and paediatric hospitals as well as private ophthalmic clinics across Australia. A cohort of 18 presumably unrelated families was identified. Twenty-two affected patients underwent clinical examination. Following DNA extraction all six exons of the RSI gene were sequenced. Results: The median age at diagnosis was 8 years (range 1-43 years); the median age at review was 14 years (range 5-63 years). The median best-corrected visual acuity upon review was 6/24 (range 6/6-1/36). Typical foveal schisis was found in 90.1% eyes examined (39/43) while peripheral schisis was present in 30% of eyes (13/43). The scotopic blue b-wave amplitude ranged between 2% and 82% of the mean normal amplitude. Five novel mutations (61G -> T, Gly21X; 103C -> T, Gln35X; 327-329del, Cys110del; 527T -> C, Phe176Ser; 573Gdel, Pro 192fs) and six previously identified missense mutations (304C -> T, Arg102Trp; 305G -> A, Arg102Gln; 336G -> C, Trp112Cys; 418G -> A, Gln140Arg; 598C -> T, Arg200Cys; 625C -> T, Arg209Cys) were found. The mutations present in codons 21 and 102 were each identified in two presumably unrelated pedigrees. One previously described point deletion (416Adel) was identified. Two pedigrees contained affected individuals where exons 2 or 3, respectively, were unable to be amplified, indicating the likely presence of a significant deletion. No mutation was found in the RSI gene in two affected individuals from different pedigrees. Conclusion: Population genetic studies of XLRS have not previously been conducted in Australia. The phenotype associated with these mutations varied. The identification of each pedigree's specific mutation allows future determination of female carrier status for genetic counselling purposes. Further study into the refinement of the XLRS phenotype as well as the degree of intrafamilial phenotypic variation is required.