Zeinab Abdollahi - Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Mohammad Amin Tabatabaiefar - Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Mohammad Hassan Emami - Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Mehrdad Zeinalian - Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

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 immunohistochemistry-MLH۱ absent, BRAF-V۶۰۰E mutation was evaluated to rule out the sporadic colorectal cancer cases. No pathogenic germline variants were found by next generation sequencing method. Multiplex ligation-dependant probe amplification technique was done to find large in/dels within MLH۱/MSH۲ genes of the probands. A two-exon deletion within MLH۱ 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.

Lynch syndrome, Colorectal cancer, Neoplastic syndromes, Hereditary, Mismatch repair gene