To describe the clinical phenotypes of four unrelated Japanese male patients w ith juvenile retinoschisis and to investigate occurrences of mutations in the RS 1 gene. Observational case series and experimental study. Fundus examinations, f luorescein angiography, and single flash electroretinography (ERG) were carried out. In one patient, optical coherence tomography (OCT) was performed. The codi ng regions of the RS1 gene that encodes retinoschisin were amplified by polymera se chain reaction (PCR). The PCR products were purified and directly sequenced. The four affected patients showed cystoid or wheel like foveal changes with a little or no fluorescein leakage and negative b wave patterns in both eyes. The OCT images of foveal retinoschisis disclosed that splitting occurs in the putat ive fibers of Henle. In three patients, we identified three different missense m utations (p.S73P, p.Y89C, p.R209C) in the functionally important discoidin domai n of the RS1 gene. The p.S73P mutation has not been previously reported. In cont rast, no nucleotide substitutions were detected in the fourth patient whose pare nts were unrelated and asymptomatic. No other member of this family for three ge nerations has had juvenile retinoschisis. Because serine 73 is conserved in the mouse ortholog and other discoidin proteins, the proline 73 allele is therefore very likely to encode a defective retinoschisin. Although the inheritance patter n is uncertain in the patient without the RS1 mutation, the clinical and ERG fin dings were indistinguishable from those of patients with RS1 mutations. This fin ding points to the genetic heterogeneity of juvenile retinoschisis. To describe the clinical phenotypes of four unrelated Japanese male patients w ith juvenile retinoschisis and to investigate the occurrence of mutations in the RS 1 gene. Observational case series and experimental study. Fundus examinations, f luorescein angiography, and single flash electroretinography (ERG) were carried The codi ng regions of the RS1 gene that encodes retinoschisin were amplified by polymera se chain reaction (PCR). The four affected patients showed cystoid or wheel like foveal changes with a little or no fluorescein leakage and negative b wave patterns in both eyes. The OCT images of foveal retinoschisis said that splitting occurs in the putat ive fibers of Henle. In three patients, we identified three different missense m utations (p.S73P, p.Y89C, p.R209C) in the functionally important discoidin domai n of the RS1 gene. The p.S73P mutation has not been previously reported. In cont rast, no nucleotide substitutions were detected in the fourth patient whose parents are unrelated and asymptomatic. No other member of this family for three ge nerations has had juvenile retinoschisis. Because serine 73 is conserved in the mouse ortholog and other discoidin proteins, the proline 73 allele is therefore very likely to encode a defective retinoschisin. Although the inheritance patter n is uncertain in the patient without the RS1 mutation, the clinical and ERG fin dings were indistinguishable from those of patients with RS1 mutations . This fin ding points to the genetic heterogeneity of juvenile retinoschisis.