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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MUTATIONS IN THE GENE ENCODING THE ALPHA SUBUNIT OF THE ROD CGMP-GATED CHANNEL IN AUTOSOMAL RECESSIVE RETINITIS PIGMENTOSA
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MUTATIONS IN THE GENE ENCODING THE ALPHA SUBUNIT OF THE ROD CGMP-GATED CHANNEL IN AUTOSOMAL RECESSIVE RETINITIS PIGMENTOSA

机译：正常渐进性视网膜色素变性中杆CGMP门通道α亚基编码基因的突变

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Mutations in the genes encoding two proteins of the retinal rod phototransduction cascade, opsin and the beta subunit of rod cGMP phosphodiesterase, cause retinitis pigmentosa (RP) in some families. Here we report defects in a third member of this biochemical pathway in still other patients with this disease. We screened 94 unrelated patients with autosomal dominant RP and 173 unrelated patients with autosomal recessive RP for mutations in the gene encoding the cu subunit of the rod cGMP-gated cation channel. Five mutant sequences cosegregated with disease among four unrelated families with autosomal recessive RP. Two of these were nonsense mutations early in the reading Frame (Glu76End and Lys139End) and one was a deletion encompassing most if not all of the transcriptional unit; these three alleles would not be expected to encode a functional channel. The remaining two mutations were a missense mutation (Ser316Phe) and a frameshift [Arg654(1-bp del)] mutation truncating the last 32 aa in the C terminus. The latter two mutations were expressed in vitro and found to encode proteins that were predominantly retained inside the cell instead of being targeted to the plasma membrane. We conclude that the absence or paucity of functional cGMP-gated cation channels in the plasma membrane is deleterious to rod photoreceptors and is an uncommon cause of RP. [References: 23]
机译：编码视网膜视杆光转导级联的两种蛋白，视蛋白和视杆cGMP磷酸二酯酶的β亚基的基因突变，在某些家庭中引起色素性视网膜炎（RP）。在这里，我们报告了该疾病其他患者中该生化途径第三部分的缺陷。我们筛选了94名常染色体显性RP无关患者和173名常染色体隐性RP无关患者的编码杆cGMP门控阳离子通道cu亚基的基因突变。在常染色体隐性RP的四个无关家族中，五个突变序列与疾病共分离。其中两个是阅读框早期的无意义突变（Glu76End和Lys139End），一个是包含大部分（如果不是全部）转录单位的缺失。这三个等位基因将不会编码一个功能通道。剩下的两个突变是一个错义突变（Ser316Phe）和一个移码[Arg654（1-bp del）]突变，截短了C末端的最后32个氨基酸。后两个突变在体外表达，发现编码主要保留在细胞内而不是靶向质膜的蛋白质。我们得出结论，质膜中不存在或缺乏功能性cGMP门控阳离子通道对杆感光器有害，并且是RP的常见原因。 [参考：23]

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