TOTAL COLOURBLINDNESS IS CAUSED BY MUTATIONS IN THE GENE ENCODING THEALPHA-SUBUNIT OF THE CONE PHOTORECEPTOR CGMP-GATED CATION CHANNEL

Total colourblindness (OMIM 216900), also referred to as rod monochrom acy (RM) or complete achromatopsia, is a rare, autosomal recessive inh erited and congenital disorder characterized by photophobia, reduced v isual acuity, nystagmus and the complete inability to discriminate bet ween colours(1). Electroretinographic recordings show that in RM, rod photoreceptor function is normal, whereas cone photoreceptor responses are absent. The locus for RM has been mapped to chromosome 2q11 (ref. 2), however the gene underlying RM has not yet been identified. Recen tly a suitable candidate gene, CNGA3, encoding the alpha-subunit of th e cone photoreceptor cCMP-gated cation channel, a key component of the phototransduction pathway, has been cloned and assigned to human chro mosome 2q11 (refs 3,4). We report the identification of missense mutat ions in CNGA3 in five families with RM. Homozygous mutations are prese nt in two families, whereas the remaining families show compound heter ozygous mutations. In all cases, the segregation pattern of the mutati ons is consistent with the autosomal recessive inheritance of the dise ase and all mutations affect amino acids that are highly conserved amo ng cyclic nucleotide gated channels (CNC) in various species. This is the first report of a colour vision disorder caused by defects other t han mutations in the cone pigment genes, and implies at least in this instance a common genetic basis for phototransduction in the three dif ferent cone photoreceptors of the human retina.