Background: X-linked retinoschisis (XLRS) is a leading cause of juvenile macular degeneration associated with mutations in the RS1 gene. XLRS has a variable expressivity in males and shows no clinical phenotype in carrier females.

Design: Clinical and molecular characterization of male and female individuals affected with XLRS in a consanguineous family.

Participants: Consanguineous Eastern European-Australian family.

Methods: Four clinically affected and nine unaffected family members were genetically and clinically characterized. Deoxyribonucleic acid (DNA) analysis was conducted by the Australian Inherited Retinal Disease Register and DNA Bank.

Main Outcome Measures: Clinical and molecular characterization of the causative mutation in a consanguineous family with XLRS.

Results: By direct sequencing of the RS1 gene, one pathogenic variant, NM_000330.3: c.304C > T, p. R102W, was identified in all clinically diagnosed individuals analysed. The two females were homozygous for the variant, and the males were hemizygous.

Conclusion: Clinical and genetic characterization of affected homozygous females in XLRS affords the rare opportunity to explore the molecular mechanisms of XLRS and the manifestation of these mutations as disease in humans.