MLH1 and MSH2 mutations in Colombian families with hereditary nonpolyposis colorectal cancer (Lynch syndrome) -: description of four novel mutations
MLH1 and MSH2 mutations in Colombian families with hereditary nonpolyposis colorectal cancer (Lynch syndrome) -: description of four novel mutations
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DOI：
10.1007/s10689-005-4523-7
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发表时间：
2005-01-01
期刊：
影响因子：
2.2
通讯作者：
Barvo, R
中科院分区：
文献类型：
--
作者：
Giraldo, A;Gómez, A;Barvo, R
这项研究在 23 个疑似遗传性非息肉病性结直肠癌 (HNPCC) 的哥伦比亚无亲缘关系家庭中寻找 MLH1 和 MSH2 基因的突变。这些家庭根据阿姆斯特丹 11 项标准或贝塞斯达指南的满足情况进行分组。我们通过单链构象多态性（SSCP）和直接DNA测序筛选了所有先证者。 11 个家庭符合阿姆斯特丹标准，11 个家庭符合贝塞斯达准则，12 个家庭符合贝塞斯达准则。在11个家系中检测到种系突变。对应的突变检出率为 48%。当仅对满足阿姆斯特丹II标准的家庭进行分析时，突变检出率上升至82%。在遵循 Bethesda 指南的家庭中，只有 8% 的突变检出率。两个不同的家族共有三个突变，相当于总共八个不同的突变，其中七个在 MLH1 基因中发现，一个在 MSH2 基因中发现。我们发现了四种之前未向 HNPCC 国际合作组报告过的突变。其中三个是致病性的：密码子 640、外显子 17 处的单碱基替换 (C > T)、密码子 619、外显子 16 和 MLH1 基因中的 G 缺失以及密码子 184、外显子 3 处的两核苷酸缺失 (TG)。此外，还检测到一个未分类的变体，即 MLH1 外显子 5 密码子 141 处的替换 (C > G)。
This study searched for mutations in the MLH1 and MSH2 genes in 23 unrelated Colombian families with suspected hereditary nonpolyposis colorectal cancer (HNPCC). The families were grouped according to the ful-fillment of the Amsterdam 11 criteria or the Bethesda guidelines. We screened all probands by single-strand conformational polymorphism (SSCP) and direct DNA sequencing. Eleven families fulfilled the Amsterdam criteria 11 and 12 families the Bethesda guidelines. Germline mutations were detected in 11 families,. which corresponds to a mutation detection rate of 48%. When only families fulfilling the Amsterdam II criteria were analyzed, the mutation detection rate rose to 82%. Only 8% of the mutation detection rate was found in families following the Bethesda guidelines. Three mutations were shared by two different families, which corresponds to a total of eight different mutations, seven of them found in the MLH1 gene and one in the MSH2 gene. We have identified four mutations that have not been previously reported to the International Collaborative Group of HNPCC. Three of these are pathogenic, a single base substitution (C > T) at codon 640, exon 17, a G deletion at codon 619, exon 16 and in the MLH1 gene and a two-nucleotide deletion (TG) at codon 184, exon 3 in the MSH2. Also, an unclassified variant, a substitution (C > G) at the codon 141, exon 5 of the MLH1, was detected.