Genetic basis of total colourblindness among the Pingelapese islanders

Complete achromatopsia is a rare, autosomal recessive disorder characterize d by photophobia, low visual acuity. nystagmus and a total inability to dis tinguish colours. In this disease, cone photoreceptors. the retinal sensory neurons mediating colour vision, seem viable but fail to generate an elect rical response to light(1,2). Achromatopsia, or rod monochromatism, was fir st mapped to 2p11-2q12 (MIM 216900; ref. 3), where it is associated with mi ssense mutations in CNGA3 (ref. 4). CNGA3 encodes the a-subunit of the cone cyclic nucleotide-gated cation channel, which generates the light-evoked e lectrical responses of cone photoreceptors(5-7). A second locus at 8q21-q22 has been identified among the Pingelapese islanders of Micronesia(8,9), wh o have a high incidence of recessive achromatopsia(10,11) (MIM 262300). Her e we narrow the achromatopsia locus to 1.4 cM and show that Pingelapese ach romatopsia segregates with a missense mutation at a highly conserved site i n CNGB3. a new gene that encodes the beta-subunit of the cone cyclic nucleo tide-gated cation channel. Two independent frameshift deletions establish t hat achromatopsia is the null phenotype of CNGB3. Combined with earlier fin dings, our results demonstrate that both alpha- and beta-subunits of the cG MP-gated channel are essential for phototransduction in all three classes o f cones.