Application of Next Generation Sequencing Approach to Molecular Diagnosis Of Hereditary Colorectal Cancer: Identification Of A Novel Heterozygous Single Nucleotide Germline Deletion In Msh2 Gene Cause Lynch Syndrome?

Volume 3 - Issue 5

Zhe Lu¹†, Lewei Yang²†, Santasree Banerjee³, Meifang Xiao¹* and Yan Zhang⁴*

Received: May 14, 2020;   Published: May 26, 2020

DOI: 10.32474/OAJOM.2020.03.000171

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Abstract

Germline mutations in DNA mismatch repair (MMR) genes including MSH2, MLH1, MSH6 and PMS2 causes Lynch syndrome (LS). Lynch syndrome (LS) is the autosomal dominantly inherited familial form of colorectal cancer (CRC) predisposing syndrome. In our present study, we identified and screen a five generation Chinese family with LS. According to the Amsterdam II criteria, clinical diagnosis has been done for the affected members of this family. In this study, we performed genetic molecular study for 79 members (11 patients and 68 unaffected members) of this five generation Chinese family and 100 normal healthy control individuals of same ethnic background. Targeted next generation sequencing and Sanger sequencing identified a novel heterozygous single nucleotide germline deletion (c.1427delC) in MSH2 gene in the proband, which is co-segregated well with the disease phenotype among all the affected family members. This novel heterozygous deletion (c.1427delC) in MSH2 gene leads to the formation of a premature stop codon (p.Pro476Leufs*6) which finally results into the formation of a truncated MSH2 protein. Our present finding expands the mutation spectrum for the MSH2 gene as well as establishes the significance of targeted next generation sequencing for identifying novel candidate mutations for patients with Lynch syndrome.

Keywords: Lynch Syndrome; MSH2 Gene; Targeted Next Generation Sequencing; Novel Mutation; DNA Mismatch Repair Gene.

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