Constitutional mismatch repair deficiency (CMMRD)是一种侵袭性和高度穿透的癌症易感倾向综合症。由于其表现形态多变，且与神经纤维瘤症有重叠现象，因此在资源有限的国家，及时诊断仍然具有挑战性。由于现有的检测方法难以实施或解释，或两者皆难，因此我们使用一种新型且相对廉价的功能基因组测定法（LOGIC），该方法最近报道在诊断CMMRD方面具有高度的敏感性和特异性。本研究报道了9名患有癌症且被怀疑患有CMMRD的患者的临床和分子特征，并强调了变异解释和免疫组化分析方面的挑战，这导致在其中6名患者中的遗传学结果存在不确定性。使用LOGIC，我们成功地确认了7名患者的CMMRD诊断，并可能排除了另外2名患者，解决了模糊的结果解释。LOGIC还允许对无症状兄弟姐妹进行预测性测试，以实现早期诊断和监测措施的实施。本研究强调了CMMRD目前的诊断标准的多样化表现和实际限制，以及国际合作在实施强大且低成本的功能测定法方面的重要性。 © 2023 作者，专属许可Springer-Verlag GmbH Germany的一部分，属于Springer Nature。

Constitutional mismatch repair deficiency (CMMRD) is an aggressive and highly penetrant cancer predisposition syndrome. Because of its variable clinical presentation and phenotypical overlap with neurofibromatosis, timely diagnosis remains challenging, especially in countries with limited resources. Since current tests are either difficult to implement or interpret or both we used a novel and relatively inexpensive functional genomic assay (LOGIC) which has been recently reported to have high sensitivity and specificity in diagnosing CMMRD. Here we report the clinical and molecular characteristics of nine patients diagnosed with cancer and suspected to have CMMRD and highlight the challenges with variant interpretation and immunohistochemical analysis that led to an uncertain interpretation of genetic findings in 6 of the 9 patients. Using LOGIC, we were able to confirm the diagnosis of CMMRD in 7 and likely exclude it in 2 patients, resolving ambiguous result interpretation. LOGIC also enabled predictive testing of asymptomatic siblings for early diagnosis and implementation of surveillance. This study highlights the varied manifestations and practical limitations of current diagnostic criteria for CMMRD, and the importance of international collaboration for implementing robust and low-cost functional assays for resolving diagnostic challenges.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.