Genetic basis of total colourblindness among the Pingelapese islanders

• Published in: Nature genetics Vol. 25; no. 3; pp. 289 - 293
• Main Authors: Sundin, Olof H, Yang, Jun-Ming, Li, Yingying, Zhu, Danping, Hurd, Jane N, Mitchell, Thomas N, Silva, Eduardo D, Maumenee, Irene Hussels
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-07-2000
• Subjects: achromatopsia; Adolescent; Amino Acid Sequence; Base Sequence; Biological and medical sciences; chromosome 8; Chromosome Mapping; Chromosomes, Human, Pair 8; Cloning; CNGA3 gene; CNGB3 gene; Color blindness; Color Vision Defects - genetics; Cyclic Nucleotide-Gated Cation Channels; Disease; DNA, Complementary; Female; Genes; Genetic aspects; Genetic Linkage; Genetics; Genomes; Humans; Ion Channels - genetics; Male; Medical sciences; Micronesia; Molecular Sequence Data; Mutation; Nucleotide sequence; Ophthalmology; Pedigree; Photoreception; Physiological aspects; Polymorphism, Genetic; Radiation; Vision disorders; Micronesia; Micronesia (Nation); Pingelap; United States > US; Genetic mapping; Human; Rod monochromatism; Nucleotide sequence; Family study; Vision disorder; Photoreceptor; Chromosome A2; Gene organization; Ionic channel; Achromatopsia; Eye disease; Contig; Mutation; Dyschromatopsia; Physical map; Polymorphism
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/77162

Complete achromatopsia is a rare, autosomal recessive disorder characterized by photophobia, low visual acuity, nystagmus and a total inability to distinguish colours. In this disease, cone photoreceptors, the retinal sensory neurons mediating colour vision, seem viable but fail to generate an electrical response to light. Achromatopsia, or rod monochromatism, was first mapped to 2p11-2q12 (MIM 216900; ref. 3), where it is associated with missense mutations in CNGA3 (ref. 4). CNGA3 encodes the alpha-subunit of the cone cyclic nucleotide-gated cation channel, which generates the light-evoked electrical responses of cone photoreceptors. A second locus at 8q21-q22 has been identified among the Pingelapese islanders of Micronesia, who have a high incidence of recessive achromatopsia (MIM 262300). Here we narrow the achromatopsia locus to 1.4 cM and show that Pingelapese achromatopsia segregates with a missense mutation at a highly conserved site in CNGB3, a new gene that encodes the beta-subunit of the cone cyclic nucleotide-gated cation channel. Two independent frameshift deletions establish that achromatopsia is the null phenotype of CNGB3. Combined with earlier findings, our results demonstrate that both alpha- and beta-subunits of the cGMP-gated channel are essential for phototransduction in all three classes of cones.