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鉴定一种新的致病性 MLH1 突变及推荐的遗传筛查策略：对三个中国 Lynch 综合征家系的研究。

Identification of a novel pathogenic MLH1 mutation and recommended genetic screening strategy: An investigation of three Chinese Lynch syndrome pedigrees.

机构信息

Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Mol Genet Genomic Med. 2020 Aug;8(8):e1295. doi: 10.1002/mgg3.1295. Epub 2020 Jun 3.

DOI:10.1002/mgg3.1295
PMID:32490589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7434735/
Abstract

BACKGROUND

Lynch syndrome (LS) is an autosomal-dominant disorder that increases the risk of many cancers. The genetic basis of LS is germline mutations in DNA mismatch repair genes.

METHODS

We performed next-generation sequencing on blood cells obtained from the members of three unrelated LS pedigrees. Immunohistochemistry staining was performed to analyze protein expression.

RESULTS

Multigene panel screening revealed three mutL homolog 1 (MLH1) pathogenic mutations (c.199G>A, c.790 + 1G>A, and c.1557_1558 + 8delGGGTACGTAA, unreported) confirmed by Sanger sequencing. Immunohistochemistry showed a loss of MLH1 protein expression. We also confirmed that the unreported mutant allele was inherited for at least three generations.

CONCLUSION

These results provide new insights into the molecular mechanisms underlying the pathogenicity of MLH1 mutations and reaffirm the importance of genetic screening for the early diagnosis of LS.

摘要

背景

林奇综合征（LS）是一种常染色体显性遗传疾病，会增加多种癌症的风险。LS 的遗传基础是 DNA 错配修复基因的种系突变。

方法

我们对三个无血缘关系的 LS 家系成员的血细胞进行了下一代测序。通过免疫组织化学染色来分析蛋白表达。

结果

多基因panel 筛查显示三个 mutL 同源物 1（MLH1）致病性突变（c.199G>A、c.790+1G>A 和 c.1557_1558+8delGGGTACGTAA，未报道），经 Sanger 测序证实。免疫组织化学显示 MLH1 蛋白表达缺失。我们还证实，未报道的突变等位基因至少遗传了三代。

结论

这些结果为 MLH1 突变的致病性的分子机制提供了新的见解，并再次证实了遗传筛查对 LS 早期诊断的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/01cd93c3c353/MGG3-8-e1295-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/483f882d4c36/MGG3-8-e1295-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/98f6ccfe4c6c/MGG3-8-e1295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/c7f29a374ea3/MGG3-8-e1295-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/c271268a97e4/MGG3-8-e1295-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/01cd93c3c353/MGG3-8-e1295-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/483f882d4c36/MGG3-8-e1295-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/98f6ccfe4c6c/MGG3-8-e1295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/c7f29a374ea3/MGG3-8-e1295-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/c271268a97e4/MGG3-8-e1295-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc67/7434735/01cd93c3c353/MGG3-8-e1295-g005.jpg

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