Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a germline mutation in the α subunit of cone transducin (GNAT2)
Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a germline mutation in the α subunit of cone transducin (GNAT2)
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DOI：
10.1136/jmg.39.9.656
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发表时间：
2002-09-01
影响因子：
4
通讯作者：
Maher, ER
中科院分区：
文献类型：
--
作者：
Aligianis, IA;Forshew, T;Maher, ER
目的：要确定色盲的分子基础，使用纯合性作图和位置候选基因analysis.Design和方法：一个大型的血亲巴基斯坦家庭，其中包含6个主题与常染色体隐性遗传完全色盲进行了确认。在排除了与两个已知的色盲基因（CNGA 3和CNGB 3）的连锁后，进行了全基因组范围的连锁screen.Results：在染色体1 p13上的标记D1 S485和D1 S2881之间的12 cM的纯合片段上检测到显著的连锁。直接序列分析的候选基因GNAT 2位于此区间内确定了移码突变外显子7（c842_843insTCAG; M280 fsX 291），隔离与diseases.Conclusions：GNAT 2基因编码锥α-transducin，G蛋白，耦合锥色素cGMP-磷酸二酯酶的光转导。尽管视锥细胞α-转导蛋白在视锥细胞光转导中具有重要作用，但GNAT 2中的突变先前未被描述。由于CNGA 3基因突变可能导致各种视网膜营养不良（完全和不完全全色盲和进行性视锥细胞营养不良），GNAT 2突变也可能被证明与其他形式的视网膜营养不良伴视锥细胞功能障碍有关。
Objective: To determine the molecular basis for achromatopsia using autozygosity mapping and positional candidate gene analysis.Design and methods: A large consanguineous Pakistani family containing six subjects with autosomal recessive complete achromatopsia was ascertained. After excluding linkage to the two known achromatopsia genes (CNGA3 and CNGB3), a genome wide linkage screen was undertaken.Results: Significant linkage was detected to a 12 cM autozygous segment between markers D1S485 and D1S2881 on chromosome 1p13. Direct sequence analysis of the candidate gene GNAT2 located within this interval identified a frameshift mutation in exon 7 (c842_843insTCAG; M280fsX291) that segregated with the disease.Conclusions: The GNAT2 gene codes for cone a-transducin, the G protein that couples the cone pigments to cGMP-phosphodiesterase in phototransduction. Although cone alpha-transducin has a fundamental role in cone phototransduction, mutations in GNAT2 have not been described previously. Since mutations in the CNGA3 gene may cause a variety of retinal dystrophies (complete and incomplete achromatopsia and progressive cone dystrophy), GNAT2 mutations may also prove to be implicated in other forms of retinal dystrophy with cone dysfunction.