【佳学基因检测】体质错配修复缺陷作为 1 型神经纤维瘤病的鉴别诊断：检测非恶性肿瘤儿童的共识指南

做基因检测费用关键点

深究基因检测与基因解码的区别与选择做了备注《J Med Genet》在. 2019 Feb;56(2):53-62.发表了一篇题目为《体质错配修复缺陷作为 1 型神经纤维瘤病的鉴别诊断：检测非恶性肿瘤儿童的共识指南》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Manon Suerink, Tim Ripperger, Ludwine Messiaen, Fred H Menko, Franck Bourdeaut, Chrystelle Colas, Marjolijn Jongmans, Yael Goldberg, Maartje Nielsen, Martine Muleris, Mariëtte van Kouwen, Irene Slavc, Christian Kratz, Hans F Vasen, Laurence Brugiѐres, Eric Legius, Katharina Wimmer等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

肿瘤靶向治疗基因检测临床应用结果

宪法性错配修复缺陷（CMMRD）是一种罕见的儿童癌症易感性综合征，由四种错配修复基因之一的双等位基因种系突变引起。除了非常高的肿瘤风险外，CMMRD 表型的特征通常是存在让人联想到 1 型神经纤维瘤病 (NF1) 的迹象。由于 NF1 体征可能在肿瘤发作之前出现，因此 CMMRD 是对怀疑患有 NF1/Legius 综合征但没有可检测到的潜在 NF1/SPRED1 种系突变的其他健康儿童的合理鉴别诊断。但是，没有指南表明何时在这种情况下咨询和测试 CMMRD。假设 CMMRD 在这些患者中很少见，并且在肿瘤发作前识别 CMMRD 的预期益处应超过在这种情况下与 CMMRD 咨询和检测相关的潜在危害，基因解码基因检测旨在制定一种策略，在疑似患有 NF1/Legius 的儿童中进行预选没有致病性 NF1/SPRED1 突变且没有明显恶性肿瘤的综合征，那些患有 CMMRD 的可能性更高的儿童。在一个跨学科研讨会上，基因解码基因检测讨论了对 CMMRD 作为 NF1 鉴别诊断的频率的估计，以及 CMMRD 咨询和检测对没有恶性肿瘤的健康儿童的潜在益处和危害。在两轮重要修订中制定和审查了咨询和测试的预选标准和策略。现有的 CMMRD 诊断标准适用于指导何时将 CMMRD 视为 NF1/Legius 综合征的鉴别诊断。此外，建议咨询和测试策略以尽量减少潜在危害。

肿瘤发生与复发转移国际数据库描述：

Constitutional mismatch repair deficiency (CMMRD) is a rare childhood cancer predisposition syndrome caused by biallelic germline mutations in one of four mismatch-repair genes. Besides very high tumour risks, CMMRD phenotypes are often characterised by the presence of signs reminiscent of neurofibromatosis type 1 (NF1). Because NF1 signs may be present prior to tumour onset, CMMRD is a legitimate differential diagnosis in an otherwise healthy child suspected to have NF1/Legius syndrome without a detectable underlying NF1/SPRED1 germline mutation. However, no guidelines indicate when to counsel and test for CMMRD in this setting. Assuming that CMMRD is rare in these patients and that expected benefits of identifying CMMRD prior to tumour onset should outweigh potential harms associated with CMMRD counselling and testing in this setting, we aimed at elaborating a strategy to preselect, among children suspected to have NF1/Legius syndrome without a causative NF1/SPRED1 mutation and no overt malignancy, those children who have a higher probability of having CMMRD. At an interdisciplinary workshop, we discussed estimations of the frequency of CMMRD as a differential diagnosis of NF1 and potential benefits and harms of CMMRD counselling and testing in a healthy child with no malignancy. Preselection criteria and strategies for counselling and testing were developed and reviewed in two rounds of critical revisions. Existing diagnostic CMMRD criteria were adapted to serve as a guideline as to when to consider CMMRD as differential diagnosis of NF1/Legius syndrome. In addition, counselling and testing strategies are suggested to minimise potential harms.