Nature Genetics
25, 289 - 293 (2000)
doi:10.1038/77162
Genetic basis of total colourblindness among the Pingelapese islanders
Olof H. Sundin1, 3, Jun-Ming Yang1, Yingying Li2, Danping Zhu2, Jane N. Hurd4, Thomas N. Mitchell2, Eduardo D. Silva1, 2
& Irene Hussels Maumenee21
Laboratory of Developmental Genetics, Johns Hopkins
University School of Medicine, Baltimore, Maryland,
USA. 2
Johns Hopkins Center for Hereditary Eye Diseases, Department
of Ophthalmology, Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA. 3
Department of Molecular Biology and Genetics, Johns
Hopkins University School of Medicine, Baltimore, Maryland
, USA. 4
1120 C Street SE, Washington DC,
USA.
Correspondence should be addressed to Olof H. Sundin osundin1@jhmi.eduComplete 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 light1,
2. 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  -subunit of the cone
cyclic nucleotide-gated cation channel, which generates the light-evoked electrical
responses of cone photoreceptors5,
6,
7. A second locus at 8q21−q22
has been identified among the Pingelapese islanders of Micronesia8,
9,
who have a high incidence of recessive achromatopsia10,
11 (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  -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 - and -subunits of
the cGMP-gated channel are essential for phototransduction in all three classes
of cones.
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