Clin Genet 1999: 55: 461–465 Printed in Ireland. All rights resered Short Report Assessment of RS1 in X-linked juvenile retinoschisis and sporadic senile retinoschisis Gehrig A, White K, Lorenz B, Andrassi M, Clemens S, Weber BHF. Assessment of RS1 in X-linked juvenile retinoschisis and sporadic se- nile retinoschisis. Clin Genet 1999: 55: 461–465. © Munksgaard, 1999 The RS1 gene is the causative gene in X-linked juvenile retinoschisis (RS). We have screened this gene for mutations in 13 patients with RS and in 7 probands with senile retinoschisis, a sporadic, later-onset form of retinoschisis. Mutations were detected in all RS patients. Of the 11 different mutations identified, six have been reported previously and five are novel. We did not find mutations in any of the senile retinoschisis patients and conclude that senile retinoschisis is not the result of germline mutations in the RS1 gene. Andrea Gehrig a , Karen White a , Birgit Lorenz b , Monika Andrassi b , Stefan Clemens c and Bernhard HF Weber a a Institut fu ¨ r Humangenetik, Biozentrum, Universita ¨t Wu ¨ rzburg, 97074 Wu ¨ rzburg, b Abteilung fu ¨ r Kinderophthalmologie, Strabismologie und Ophthalmogenetik, Klinikum der Universita ¨ t, 93042 Regensburg, c Klinik und Poliklinik fu ¨r Augenheilkunde, Universita ¨ t Greifswald, 17489 Greifswald, Germany Key words: mutation analysis – RS1 – senile retinoschisis – X-linked juvenile retinoschisis Corresponding author: Bernhard HF Weber, Institut fu ¨ r Humangenetik, Biozentrum, Am Hubland, D-97074 Wu ¨ rzburg, Germany. Fax: +49 931 8884069; e-mail: bweb@biozentrum.uni-wuerzburg.de Received 29 December 1998, revised and accepted for publication 10 February 1999 X-linked juvenile retinoschisis (RS; OMIM c 312700) is a rare, early-onset disorder causing pro- gressive visual loss in males. The disease is charac- terized by schisis, or splitting, of the nerve fiber and ganglion cell layers of the retina (1). Lesions are typically foveal, but 50% of patients also de- velop a peripheral schisis (2). RS is clinically vari- able, with symptoms ranging from slightly reduced visual acuity to more significant complications, such as retinal detachment or vitreous hemorrhage. Although the pathogenesis of RS is not well under- stood, the specific b-wave abnormalities on electro- retinogram (ERG) suggest that the disease is due to a defect in the Mu ¨ ller cells, the primary glial cells of the retina that support retinal structure and metabolism (3, 4). RS1, a retina-specific gene underlying RS pathology, was identified recently using positional cloning methods (5), and 86 different mutations have been described (5–8). A majority of the re- ported mutations are missense mutations and are located within an evolutionarily conserved dis- coidin domain that is thought to be involved in cell – cell interaction (9). Retinoschisis also occurs sporadically in a ‘se- nile’ form and is suggested to be a common condi- tion based on findings in one series demonstrating senile retinoschisis in approximately 4% of unse- lected ophthalmologic patients (10). Clinically, se- nile retinoschisis is differentiated from RS by an adult onset of symptoms, no specific changes in the macula, an equal sex ratio of affected individuals, a generally good prognosis for visual acuity, and a negative family history (10, 11). Senile retinoschisis is divided into two types, one more benign ‘periph- eral’ form and another more rapidly progressive ‘reticular’ or ‘bullous’ form (12). Histologically, the bullous form is similar to RS, whereas the periph- eral form is distinct in that the schisis occurs in the outer plexiform layer (12, 13). 461