Document Type : Brief Report

Authors

1 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Pediatric Inherited Disease Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

3 Poursina Hakim Digestive Diseases Research Center, Isfahan, Iran

4 Iranians Cancer Control Charity Institute (MACSA), Isfahan, Iran

Abstract

Lynch syndrome (LS) predisposes individuals to early-onset colorectal and other Lynch-associated cancer. This disorder is an autosomal dominant genetic disturbance caused by germline mutations in one of the mismatch repair genes. Different clinical and molecular criteria are used to diagnose LS. Microsatellite instability testing and immunohistochemistry are two widely used methods for the molecular screening of LS-associated cancers. According to the immunohistochemistry and Microsatellite instability testing, we introduce three Persian families with Lynch-like syndrome (LLS) who met clinical Amsterdam-II criteria and their probands were mismatch repair deficient. In the case of IHC-MLH1 absent, BRAF-V600E mutation was evaluated to rule out the sporadic colorectal cancer cases. No pathogenic germline variants were found by next generation sequencing method. MLPA technique was done to find large in/dels within MLH1/MSH2 genes of the probands. A two-exon deletion within MLH1 gene was eventually identified in one of the patients. Finally, we have represented a molecular pipeline to diagnose LLS based on literature review and the introduced cases.

Keywords

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.30476/mejc.2022.92251.1650

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