Investigation,analysis And Risk Management Of Three Families With Lynch Syndrome

Objective:.To retrospectively investigate the clinical characteristics of three families with Lynch syndrome,predict and analyze the mutation sites,and summarize the diagnosis and treatment experience and risk management of Lynch syndrome.Methods: A total of 369 patients with colorectal cancer from 2015 to 2017 were interviewed.Forty-five high-risk populations of hereditary colorectal cancer were screened out.Eight of them underwent genetic testing and three were diagnosed with Lynch syndrome..The clinical data of the 3 family members with Lynch syndrome were collected and their pedigrees were drawn.The genetic status of LS family members was detected by target region second-generation sequencing and Sanger method,and functional prediction analysis of mutation sites was carried out by combining immunohistochemistry and bioinformatics methods.To summarize the clinical characteristics,diagnosis,treatment and risk control of the disease.Results: The three families diagnosed were all MLH1 rare mutations,one of which was reported for the first time.Combined with clinical data and functional analysis,it was predicted that all mutations in three families were pathogenic mutations.Family 1: splicing site mutation,which can cause partial amino acid loss in exon 9 and 10 of MLH1 protein.This family has a total of 36 people in five generations,and 10 people in four consecutive generations have developed diseases(including 8 cases of colon cancer and 2 cases of ovarian cancer).13 people in this family have received the detection of this locus,8 of whom are actually carriers of the mutated gene(5 have developed diseases).Family 2: splicing site mutation(new site),which can lead to the formation of new transcripts,resulting in protein structural changes and loss of function;In this family,there were 22 people in six generations,and 10 people had been infected for three consecutive generations(6 cases of colon cancer and 4 other malignant tumors).Family 3: missense mutation.This site is highly conserved,and the mutant protein can significantly reduce the repair function of mismatches.There were 17 people in this family for 3 generations,and 11 people had been diagnosed in 2 consecutive generations(including 8 cases of colon cancer and 3 cases of other malignant tumors).Only the proband in this family received genetic testing.Conclusions: Families with multiple members suffering from tumors,especially colorectal tumors and female reproductive system tumors,should be alert to the risk of hereditary tumors,including Lynch syndrome,and should be screened for their genetic background.Positive carriers should be included in risk control.