Purpose: X-linked retinoschisis (XLRS) is a leading cause of juvenile macular degeneration associated with mutations in the RS1 gene. XLRS has variable expressivity in males and shows no clinical phenotype in carrier females. Having identified two female siblings clinically affected with XLRS in a consanguineous family, we sought to investigate the causative mutations. Methods: A consanguineous Australian family, referred to the Australian Inherited Retinal Disease Register containing individuals clinically diagnosed with XLRS who had not before participated in similar research, were clinically phenotyped and analysed for disease causing mutations in the RS1 gene. Two affected males and two affected female siblings were available for analysis. Results: Sequencing of the male proband identified a known disease-causing variant, c.304C>T encoding a p.Arg102Trp substitution in the phylogenetically conserved discoidin domain of the retinoschisin protein. Further analyses confirmed the absence of wild-type signal at position c.304 in all affected family members. The two affected males are assumed to be hemizygous, whilst the two affected females are assumed to be homozygous. The mother and father of the affected sisters were found to be heterozygous and hemizygous for this familial variant respectively. Clinical phenotyping revealed the affected females had bilateral visual loss at an earlier age compared to their affected male counterparts. Conclusion: Affected homozygous females are exceptionally rare in x-linked recessive disorders. This XLRS consanguineous family containing affected females presented a novel opportunity to further explore the molecular mechanisms of XLRS and the manifestation of these mutations as disease in humans.
|Number of pages||1|
|Journal||Clinical and Experimental Ophthalmology|
|Publication status||Published - Nov 2014|
|Event||The Royal Australian and New Zealand College of Ophthalmologists, 46th Annual Scientific Congress - Brisbane, Australia|
Duration: 22 Nov 2014 → 26 Nov 2014