X-linked retinoschisis with point mutations in the XLRS1 gene

Background: X-linked retinoschisis (XLRS) is a relatively rare vitreoretina l dystrophy that causes visual loss in young men. Recently, a gene responsi ble for this disease, designated XLRS1, was identified, and several deleter ious gene mutations were reported. Objective: To analyze Japanese patients clinically diagnosed as having XLRS formutational changes in the XLRS1 gene. Methods: Ten patients with XLRS underwent full ophthalmologic examination, including slitlamp biomicroscopy and dilated funduscopy. Genomic DNA was is olated from leukocytes, and all exons of the XLRS1 gene were amplified by p olymerase chain reaction and analyzed using a direct sequencing method. Results: Point mutations in the XLRS1 gene were identified in all 10 patien ts. The mutations were identical in each of 2 pairs of brothers. Six of the point mutations represented missense mutations, 1 was a nonsense mutation, and 1 was a frameshift mutation. Five of the mutations are newly reported herein. Conclusions: The discovery of new point mutations in this study increases t he available information regarding the spectrum of genetic abnormalities an d clinical manifestations of XLRS. However, the limited data failed to reve al a correlation between mutation and disease phenotype. Clinical Relevance: Identification of mutations in the XLRS1 gene and expan ded information on clinical manifestations will facilitate early diagnosis, appropriate early therapy, and genetic counseling regarding the prognosis of XLRS.