Retinitis pigmentosa and allied diseases. Implications of genetic heterogeneity.

in response to a genetic defect, the human retina has two major categories of response: to degenerate or not to work well. Ophthalmologists and vision scientists have been successful during the last century in discovering variations in clinical course, symptoms, funduscopic appearance, and measurements of visual function that distinguish scores of hereditary retinal diseases. Most of this categorization was accomplished with very few firm clues as to the biochemical basis for the degenerations or dysfunctions that were under scrutiny, although lack of precise knowledge did not stop investigators from proposing numerous explanatory theories. Now that molecular genetics and molecular biology techniques are revealing the precise mutations causing some of these diseases, it is becoming evident that many of the clinically "distinct" entities overlap etiologically. As examples, it has been found recently that X-linked familial exudative vitreoretinopathy can be caused by a defect in the Norrie disease gene and that defects in the rhodopsin gene can cause autosomal dominant retinitis pigmentosa, autosomal recessive retinitis pigmentosa, or congenital stationary night blindness. Also, some diseases clinically categorized under a single heading are heterogeneous genetically. Illustrative examples of this latter phenomenon are retinitis pigmentosa and allied retinal degenerations, the heterogeneity of which will be the subject of this commentary.