PMS2 基因中意义不明的变异导致 DNA 错配修复失活。
Inactivation of DNA mismatch repair by variants of uncertain significance in the PMS2 gene.
机构信息
Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands.
出版信息
Hum Mutat. 2013 Nov;34(11):1477-80. doi: 10.1002/humu.22426. Epub 2013 Sep 11.
Abstract
Lynch syndrome (LS) is a common cancer predisposition caused by an inactivating mutation in one of four DNA mismatch repair (MMR) genes. Frequently a variant of uncertain significance (VUS), rather than an obviously pathogenic mutation, is identified in one of these genes. The inability to define pathogenicity of such variants precludes targeted healthcare. Here, we have modified a cell-free assay to test VUS in the MMR gene PMS2 for functional activity. We have analyzed nearly all VUS in PMS2 found thus far and describe loss of MMR activity for five, suggesting the applicability of the assay for diagnosis of LS.
摘要
林奇综合征（LS）是一种常见的癌症易感性，由四个 DNA 错配修复（MMR）基因之一的失活突变引起。通常，在这些基因之一中会发现一种意义不明的变体（VUS），而不是明显的致病性突变。由于无法确定此类变体的致病性，因此无法进行有针对性的医疗保健。在这里，我们修改了一种无细胞测定法来测试 MMR 基因 PMS2 中的 VUS 的功能活性。我们分析了迄今为止在 PMS2 中发现的几乎所有 VUS，并发现其中五个的 MMR 活性丧失，表明该测定法可用于 LS 的诊断。
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本文引用的文献
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J Med Genet. 2013 Aug;50(8):552-63. doi: 10.1136/jmedgenet-2012-101511. Epub 2013 May 24.
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Calibration of multiple in silico tools for predicting pathogenicity of mismatch repair gene missense substitutions.多种用于预测错配修复基因错义替换致病变异体预测的计算机模拟工具的校准。
Hum Mutat. 2013 Jan;34(1):255-65. doi: 10.1002/humu.22214. Epub 2012 Oct 22.
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