Lynch综合征(LS)是一种常染色体显性遗传的癌症综合征。它可能是由几个基因的突变引起的,包括MLH1,MSH2,MSH6,PMS2,MLH3和MSH3,它们负责DNA错配修复,LS影响3-5%的结直肠癌(CRC)患者。LS在几个不同的地方与癌症的高风险相关,尽管最常见的受影响区域是结肠(20-70%的风险),子宫内膜(15-70%的风险),胃(6-13%的风险)和卵巢(4-12%的风险)。在本报告中,描述了在MSH2基因中检测到致病性变异的LS家族性病例。先证者是一名男性,在25岁时被诊断患有CRC。家谱分析显示,共有7名受影响的亲属(包括先证者),其中一个(我是相对的,母亲)患有同步癌症(子宫内膜和卵巢癌),另外五个(II和III度相关)患有卵巢癌。使用下一代测序的遗传分析在先证者和他的母亲中检测到MSH2基因中的杂合种系突变(c.13861G>A),确认LS的诊断。在先证者的无症状亲属(II度亲属,叔叔),发现了相同的家族性突变.随后对该亲戚进行预防性结肠镜检查显示早期CRC。该案例证实了特定基因分析的必要性,除了遗传咨询,遗传性癌症综合征。对LS患者进行积极的遗传预防可以在其他位置早期发现原发性癌症,和亲属的症状前遗传分析是早期诊断的一种选择。
Lynch syndrome (LS) is an autosomal dominant cancer syndrome. It can be caused by mutations of several genes, including MLH1, MSH2, MSH6, PMS2, MLH3 and MSH3, which are responsible for DNA mismatch repair, and LS affects 3-5% of patients with colorectal cancer (CRC). LS is associated with a high risk of cancer in several different locations, although the most commonly affected regions are the colon (20-70% risk), endometrium (15-70% risk), stomach (6-13% risk) and ovaries (4-12% risk). In the present report, the familial
case of LS with a detected pathogenic variant in the MSH2 gene is described. The proband was a male who was diagnosed with CRC at the age of 25 years. Genealogy analysis revealed a total of seven affected relatives (including the proband), one of whom (I degree relative, mother) had synchronous cancers (endometrial and ovarian) and five others (of II and III degree relation) had ovarian cancer. Genetic analysis using next generation sequencing detected a heterozygous germline mutation in the MSH2 gene (c.1386 + 1G >A) in the proband and his mother, confirming the diagnosis of LS. The results of the recommended genetic test in an asymptomatic relative of the proband (II degree relative, uncle), found the same familial mutation. Subsequent prophylactic colonoscopy of this relative revealed early stage CRC. The presented
case confirms the need for specific genetic analysis, alongside genetic counseling, in hereditary cancer syndromes. Active genetic prophylaxis in patients with LS allows early detection of primary cancers in other locations, and pre-symptomatic genetic analysis of relatives is an option for early diagnosis.