Mutations of the XLRS1 gene cause abnormalities of photoreceptor as well as inner retinal responses of the ERG

Intensity-series rod and cone ERGs were recorded in 19 patients with XLRS a nd 26 control eyes. All patients were examined by one ophthalmologist and d iagnosed on the basis of fundus appearance and evidence of the disease in o ther males in the same family. Mutations in the XLRS1 gene have been identi fied in 15 of the patients. Dark-adapted ERGs were significantly different from controls for all test conditions and for both a-wave and b-wave respon ses. Abnormalities were detectable in all patients but there was considerab le variation in the severity of abnormality. One third of the patients had the dark-adapted 'negative-wave' response typically associated with inner r etinal disorder, but about one third showed only mild depression of the b-w ave while the remainder had abnormally low a-waves in addition to depressed b-waves. Light-adapted responses were also affected and both a-wave and b- wave responses differed significantly from controls, but the `negative-wave ' response was not seen in any patient. The severity of the ERG abnormality did not correlate with the classification of fundus appearance or patient age suggesting that retinal function is relatively stable throughout life. The severity of ERG abnormalities did not correlate with the type of mutati on and responses could differ between affected males within the same family . These results indicate considerable heterogeneity of ERG response without clinical, age or genetic correlate. The abnormal a-wave responses indicate that photoreceptor as well as inner retinal layer function may be affected in XLRS, at least in some patients.