Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex
Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex
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DOI：
10.1002/humu.21451
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发表时间：
2011-04-01
期刊：
影响因子：
3.9
通讯作者：
Nellist, Mark
中科院分区：
文献类型：
--
作者：
Hoogeveen-Westerveld, Marianne;Wentink, Marjolein;Nellist, Mark
错义变化和小的框内缺失和插入对蛋白质功能的影响不容易预测，并且在有遗传疾病风险的个体中识别此类变体可能使遗传咨询复杂化。一种选择是进行功能测试，以评估变体是否影响蛋白质功能。我们已经使用这种策略来表征在患有或疑似患有多发性硬化症（TSC）的个体中在TSC 1和TSC 2基因中鉴定的变体。在这里，我们提出了我们的45 TSC 1和107 TSC 2变体的功能研究的概述。使用标准化方案，我们将16种TSC 1变体和70种TSC 2变体归类为致病性。此外，我们确定了8个假定的剪接位点突变（5个TSC 1和3个TSC 2）。其余24个TSC 1和34个TSC 2变异体被归类为可能中性。Hum Mutat 32：424-435，2011年。(C)2011 Wiley-Liss，Inc.
The effects of missense changes and small in-frame deletions and insertions on protein function are not easy to predict, and the identification of such variants in individuals at risk of a genetic disease can complicate genetic counselling. One option is to perform functional tests to assess whether the variants affect protein function. We have used this strategy to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC). Here we present an overview of our functional studies on 45 TSC1 and 107 TSC2 variants. Using a standardized protocol we classified 16 TSC1 variants and 70 TSC2 variants as pathogenic. In addition we identified eight putative splice site mutations (five TSC1 and three TSC2). The remaining 24 TSC1 and 34 TSC2 variants were classified as probably neutral. Hum Mutat 32: 424-435, 2011. (C) 2011 Wiley-Liss, Inc.