Open AccessIdentification of a novel pathogenic MLH1 mutation and recommended genetic screening strategy: An investigation of three Chinese Lynch syndrome pedigrees
Author(s) -
Li Fan,
Xia Yunwei,
Wang Guoguang,
Tang Chaoyang,
Zhan Tian,
Shen Jian,
Zhang Jianping
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1295
Subject(s) - sanger sequencing , mlh1 , genetics , lynch syndrome , pedigree chart , biology , allele , mutation , dna mismatch repair , germline mutation , gene , pms2 , germline , dna repair
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.