A RANGE OF CLINICAL PHENOTYPES ASSOCIATED WITH MUTATIONS IN CRX, A PHOTORECEPTOR TRANSCRIPTION-FACTOR GENE

Mutations in the retinal-expressed gene CRX (cone-rod homeobox gene) h ave been associated with dominant cone-rod dystrophy and with de novo Leber congenital amaurosis. However, CRX is a transcription factor for several retinal genes, including the opsins and the gene for interpho toreceptor retinoid binding protein. Because loss of CRX function coul d alter the expression of a number of other retinal proteins, we scree ned for mutations in the CRX gene in probands with a range of degenera tive retinal diseases. Of the 294 unrelated individuals screened, we i dentified four CRX mutations in families with clinical diagnoses of au tosomal dominant cone-rod dystrophy, late-onset dominant retinitis pig mentosa, or dominant congenital Leber amaurosis (early-onset retinitis pigmentosa), and we identified four additional benign sequence varian ts. These findings imply that CRX mutations may be associated with a w ide range of clinical phenotypes, including congenital retinal dystrop hy (Leber) and progressive diseases such as cone-rod dystrophy or reti nitis pigmentosa, with a wide range of onset.