Abstract
Purpose :
To describe the phenotype and genotype of a family cohort (observational study, n=6) of X-linked retinoschisis in an Irish population with a novel RS1 mutation.
Methods :
Patients were recruited as part of the Irish national genetic screening registry for inherited retinal degenerations. This screening program includes clinical history and examination with retinal imaging, electrophysiology, visual field testing and genetic analysis. Six patients (age 62y – 74y) were identified with X-linked retinoschisis (five brothers, one male first cousin). Next generation sequencing (NGS) was performed for each patient. Investigation into the family history revealed 5 grandsons and a further maternal male first cousin that are affected.
Results :
All had a history of visual acuity and colour vision disturbance from childhood. There was significant phenotypic variability between the six subjects. The youngest and least severely affected patient had one eye enucleated; the remaining eye had a normal macular appearance, with vitreous strands. The eldest and most severely affected patient had advanced macular atrophy. The four patients of intermediate age and severity had a more classic macular retinoschisis pattern of retinal splitting. NGS detected a novel RS1 gene mutation (X chromosome); this was a single base change (c.413C>A) in exon 5. This mutation had not been previously submitted to the Retinoschisis Consortium, but a different mutation at this codon (c.412A>G) has been describe, which leads to a deficiency of the retinoschisin protein.
Conclusions :
This family has a novel gene mutation in the RS1 gene with clinical retinoschisis. The next step is to investigate the male children of these patients’ daughters for retinoschisis and this RS1 mutation. We aim to collaborate with current research in the development of gene therapy for treatment of RS1 gene mutations. Those with more advanced macular atrophy will have limited potential for improvement; however, the primary beneficiaries of gene therapy are the younger generation. With early clinical and genetic detection of X-linked retinoschisis phenotype/genotype in genetically predisposed individuals, permanent central visual loss may be prevented.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.