THE EFFECTS OF DYSTROPHIN GENE-MUTATIONS ON THE ERG IN MICE AND HUMANS

Purpose. The authors' earlier findings of a negative electroretinogram (ERG) in a boy with Duchenne muscular dystrophy (DMD) led them to inv estigate dystrophin gene deletions and ERGs in five boys with DMD. The authors wanted to determine whether there were similar ERG findings i n an animal model for DMD, the mdx mouse. Methods. Ganzfeld ERGs were recorded in five boys with DMD after a complete ophthalmic examination . The dystrophin gene was analyzed by Southern blot hybridization. ERG s were recorded in anesthetized mdx and control mice with a modified G rass photostimulator (Grass Instrument Company, Quincy, MA). Results. Ophthalmic examinations in all five boys had normal findings, yet an a bnormal negative ERG was recorded for each subject. The subjects' gene deletions were variable, ranging from large deletions to no detectabl e deletions. The ERGs of the mdx mice were normal and did not differ s ignificantly from those of the control mice. Conclusions. The authors believe the unique ERG recorded for the human subjects is a manifestat ion of DMD associated with defects at the dystrophin gene locus and re presents a new clinical. entity. The ERG of the mdx mouse may be spare d for several reasons, including milder effects of the mouse gene defe ct, differences in muscle and retinal gene product, or species differe nces in the biochemical role of dystrophin. The ERG shows promise of b ecoming a noninvasive diagnostic tool for DMD and its milder allelic f orms.