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In considering inherited disease, one important distinction is between diseases with a clear, unequivocal genetic cause and other diseases whose occurrence is influenced by genetic factors, but whose causes are multifactorial. The first type, simple or Mendelian inherited diseases, typically have a distinct mode of inheritance-autosomal dominant, autosomal recessive or X-linked-and are the result of rare, pathogenic mutations with high penetrance (presence of the mutation or mutations has a high likelihood of causing disease). Examples of Mendelian diseases that include neovascularization are X-linked Norrie’s disease (1) and autosomal dominant glaucoma caused by mutations in myocilin (2). Even “simple” inherited diseases are genetically complicated, as mutations in different genes may cause the same disease, and different mutations in the same gene may cause different diseases. However, it is reasonable to assume that the cause of a Mendelian disease in a given individual and family is one mutation only (or two, if recessive) in a specific gene.

Of the 14 loci so far associated with autosomal dominant retinitis pigmentosa (RP), the most recently cloned gene is the one responsible for RP17 which occurs in six South African families comprising 187 individuals. Of these, 60 individuals are currently affected with RP and 16 are at risk by virtue of their relatedness to a known mutation carrier. The gene responsible for RP17 is carbonic anhydrase IV (CA4), one of a family of carbonic anhydrases which are involved in the interconversion of carbon dioxide and carbonic acid (11). The proposed mechanism of disease suggests that a drug-based treatment may be possible.