Genetic basis of total colourblindness among the Pingelapese islanders
Genetic basis of total colourblindness among the Pingelapese islanders
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DOI：
10.1038/77162
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发表时间：
2000-07-01
期刊：
影响因子：
30.8
通讯作者：
Maumenee, IH
中科院分区：
文献类型：
--
作者：
Sundin, OH;Yang, JM;Maumenee, IH
完全性色盲是一种罕见的常染色体隐性遗传疾病，以视物恐怖、视力低下为特征。眼球震颤和完全不能辨别颜色在这种疾病中，视锥细胞。调节色觉的视网膜感觉神经元似乎是可行的，但不能对光产生电反应（1，2）。色盲或视杆细胞单色性首先定位于2 p11 - 2 q12（MIM 216900;参考文献3），在那里它与CNGA 3的错义突变相关（参考文献4）。CNGA 3编码视锥环核苷酸门控阳离子通道的α亚基，其产生视锥光感受器的光诱发电响应（5-7）。第二个基因座位于8 q21-q22，在密克罗尼西亚的平格拉岛人中发现（8，9），他们隐性色盲发病率很高（10，11）（MIM 262300）。在这里，我们缩小了色盲基因座到1.4厘米，并显示Pingelapese色盲分离与错义突变在CNGB 3中的一个高度保守的位点。一个新的基因，编码锥环核苷酸门控阳离子通道的β亚基。两个独立的移码缺失确定色盲是CNGB 3的无效表型。结合早期的研究结果，我们的研究结果表明，α和β亚基的cGMP门控通道是必不可少的光转导在所有三类锥。
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(1,2). 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 a-subunit of the cone cyclic nucleotide-gated cation channel, which generates the light-evoked electrical responses of cone photoreceptors(5-7). A second locus at 8q21-q22 has been identified among the Pingelapese islanders of Micronesia(8,9), who have a high incidence of recessive achromatopsia(10,11) (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 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.