A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate
A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate
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锥体环核苷酸门控阳离子通道中的移码插入导致来自农村分离株的近亲家庭完全色盲
DOI：
10.1038/sj.ejhg.5200856
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发表时间：
2002
影响因子：
5.2
通讯作者：
M. Alliende
中科院分区：
文献类型：
--
作者：
C. Rojas;L. S. María;José Luís Santos;F. Cortés;M. Alliende
完全色盲具有遗传异质性，并因 CNGA3 或 CNGB3 基因突变而分离，这些基因分别编码视锥细胞中表达的环核苷酸门控 (CNG) 阳离子通道的 α 和 β 亚基。在智利中部的一个农村分离株中发现了该疾病的高发病率（六十分之一）。我们排除了先前报道的有五名受影响成员的近亲亲属的突变。使用短串联重复多态性 (STRP) 标记的基因型分析为寻找 CNGB3 的致病突变提供了证据。鉴定出位于外显子 4 中腺苷 (A5) 重复序列两侧的两个序列变异：c.492_493insT 和 c.488A>G。移码突变在外显子 5 中产生两个连续的终止密码子，这会导致翻译过早终止。严重截短的 β 亚基可能会导致锥体 CNG 通道失去功能，并导致该类动物完全色盲。
Complete achromatopsia is genetically heterogeneous and segregates with mutations in CNGA3 or CNGB3 genes, which respectively encode for α- and β-subunits of the cyclic-nucleotide-gated (CNG) cation channel expressed in cone photoreceptors. High incidence of the disease (1 in 60) was detected in a rural isolate in central Chile. We excluded previously reported mutations in a consanguineous kindred with five affected members. Genotype analysis with short tandem repeat polymorphic (STRP) markers provided evidence to search for the causative mutation in CNGB3. Two sequence variations, c.492_493insT and c.488A>G, flanking an adenosine (A5) repeat in exon 4 were identified. The frameshift mutation creates two consecutive stop codons in exon 5 that would induce premature translation termination. The severely truncated β-subunit is likely to render a nonfunctional cone CNG channel and cause total colour blindness in this kindred.
使用 DNA 合并将全色盲与 2 号染色体进行纯合性映射。
影响因子：
3.5
作者：
Arbour,NC;Zlotogora,J;Knowlton,RG;Merin,S;Rosenmann,A;Kanis,AB;Rokhlina,T;Stone,EM;Sheffield,VC
通讯作者：
Sheffield,VC