MUTATIONS IN THE CANDIDATE GENE FOR NORRIE DISEASE
MUTATIONS IN THE CANDIDATE GENE FOR NORRIE DISEASE
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DOI：
10.1093/hmg/1.7.461
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发表时间：
1992-10-01
影响因子：
3.5
通讯作者：
ROPERS, HH
中科院分区：
文献类型：
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作者：
BERGER, W;VANDEPOL, D;ROPERS, HH
最近，我们和其他人已经分离出一个X连锁诺里病（ND）的候选基因，该基因在一些患者中被发现被删除或破坏。作为鉴定ND基因点突变的先决条件，我们已经建立了该基因的外显子-内含子结构。采用单链构象多态性（SSCP）技术分析了17例无亲和关系患者和15例对照者启动子区、外显子1和2以及外显子3编码部分的PCR产物。在12例患者中检测到PCR片段的改变，并通过直接测序进行了详细的研究。他们发现了11种不同的突变，除了一种突变外，其他突变都可能导致预测蛋白质的显著结构变化。这些发现，以及健康对照中功能相关碱基变化的缺失，强调了该候选基因在诺里病中的因果作用，并为可靠的诊断和携带者检测铺平了道路。
Recently, we and others have isolated a candidate gene for X linked Norrie disease (ND) which was found to be deleted or disrupted in several patients. As a prerequisite for the identification of point mutations in the ND gene we have established the exon-intron structure of this gene. In 17 unrelated patients and 15 controls, PCR products derived from the promoter region, exons 1 and 2 as well as the coding part of exon 3 were analysed with the single strand conformation polymorphism (SSCP) technique. In 12 patients altered PCR fragments were detected which were studied in detail by direct sequencing. Eleven different mutations were found, and all but one are likely to give rise to significant structural changes in the predicted protein. These findings, and the absence of functionally relevant base changes in healthy controls, emphasize the causal role of this candidate gene in Norrie disease and pave the way for reliable diagnosis and carrier detection.