Lynch syndrome (LS) is a condition which predisposes individuals primarily to early-onset colorectal and endometrial cancer. LS is characterized by a germline pathogenic variant in one of the MMR (MisMatch Repair) gene, inducing a phenotype of microsatellite instability in the tumor, which may be associated with a loss of expression of MMR proteins detected by standard immunohistochemistry on tumor tissue. Most of the time, LS is inherited from a parent in whom the condition may not be known due to incomplete penetrance, but de novo pathogenic variant is a rare occurrence. Here, we describe the case of a 52-year-old woman with no family history of LS, referred to the genetics department for colorectal cancer at the age of 50. Genetic analysis revealed a de novo germline pathogenic variant in the MSH6 gene. To date, this case is only the second report of a de novo pathogenic variant in the MSH6 gene in Lynch syndrome. De novo mutations have been extensively studied over the past years, but little is known about their origin and mechanism of occurrence in MMR genes. However, knowledge of mutation status allows better cancer risk management for the patient and an appropriate genetic testing and counseling for her family.

林奇综合征 (LS) 是一种使个体主要易患早发性结直肠癌和子宫内膜癌的疾病。LS 的特征在于其中一个 MMR（MisMatch Repair）基因中的种系致病变异，诱导肿瘤中微卫星不稳定性的表型，这可能与肿瘤组织上标准免疫组织化学检测到的 MMR 蛋白表达缺失有关。大多数情况下，LS 遗传自父母，由于不完全外显率，其病情可能未知，但从头致病性变异很少发生。在这里，我们描述了一名没有 LS 家族史的 52 岁女性的病例，她在 50 岁时因结直肠癌转诊至遗传学部门。遗传分析揭示了MSH6中的从头生殖系致病变异基因。迄今为止，该病例只是林奇综合征中MSH6基因从头致病变异的第二次报告。在过去的几年中，从头突变得到了广泛的研究，但对于它们在 MMR 基因中的起源和发生机制知之甚少。然而，对突变状态的了解可以为患者提供更好的癌症风险管理，并为她的家人提供适当的基因检测和咨询。