PDF(Pubmed)
Abstract：
UNASSIGNED: Lynch syndrome is caused by a germline mutation in mismatch repair (MMR) genes, leading to the loss of expression of MMR heterodimers, either MLH1/PMS2 or MSH2/MSH6, or isolated loss of PMS2 or MSH6. Concurrent loss of both heterodimers is uncommon, and patients carrying pathogenic variants affecting different MMR genes are rare, leading to the lack of cancer screening recommendation for these patients.Case presentation:Here, we reported a female with a family history of Lynch syndrome with MLH1 c.676C > T mutation. She developed endometrial cancer at 37 years old, with loss of MLH1/PMS2 expression. Immunohistochemical staining on tumor samples incidentally detected the additional loss of MSH6 expression. Whole exome sequencing on genomic DNA from peripheral blood revealed MSH6 c.2731C > T mutation, which was confirmed to be inherited from her mother, who had an early-onset ascending colon cancer without cancer family history.
UNASSIGNED: This is a rare case of the Lynch syndrome harboring germline mutations simultaneously in two different MMR genes inherited from two families with Lynch syndrome. The diagnosis of endometrial cancer at the age less than 40 years is uncommon for Lynch syndrome-related endometrial cancer. This suggests an earlier cancer screening for patients carrying two MMR mutations.
UNASSIGNED: This is a rare case of the Lynch syndrome harboring germline mutations simultaneously in two different MMR genes inherited from two families with Lynch syndrome. The diagnosis of endometrial cancer at the age less than 40 years is uncommon for Lynch syndrome-related endometrial cancer. This suggests an earlier cancer screening for patients carrying two MMR mutations.
摘要：
■林奇综合征是由错配修复（MMR）基因的种系突变引起的，导致MMR异源二聚体的表达丧失，MLH1/PMS2或MSH2/MSH6，或PMS2或MSH6的隔离损失。两种异二聚体的同时丢失并不常见，携带影响不同MMR基因的致病变异的患者很少见，导致这些患者缺乏癌症筛查建议。案例介绍:这里,我们报道了1例女性,有Lynch综合征家族史,MLH1c.676C>T突变.她37岁时患上子宫内膜癌,MLH1/PMS2表达缺失。对肿瘤样品的免疫组织化学染色偶然检测到MSH6表达的额外损失。外周血基因组DNA的全外显子组测序显示MSH6c.2731C>T突变，被证实是从她母亲那里继承的,没有癌症家族史的早发性升结肠癌患者。
这是一例罕见的Lynch综合征病例，在遗传自两个Lynch综合征家族的两个不同MMR基因中同时存在种系突变。对于Lynch综合征相关的子宫内膜癌，年龄小于40岁的子宫内膜癌的诊断并不常见。这表明对携带两个MMR突变的患者进行更早的癌症筛查。
这是一例罕见的Lynch综合征病例，在遗传自两个Lynch综合征家族的两个不同MMR基因中同时存在种系突变。对于Lynch综合征相关的子宫内膜癌，年龄小于40岁的子宫内膜癌的诊断并不常见。这表明对携带两个MMR突变的患者进行更早的癌症筛查。
