{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:13:06Z","timestamp":1793121186841,"version":"4.5.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to characterize the pathogenic variants in three colon cancer families suspected of Lynch syndrome (LS), providing experimental evidence for precision screening and genetic counseling of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three suspected LS families were first identified, and subsequently, immunohistochemical analysis was performed on colon tissue samples from probands to assess the expression of four DNA mismatch repair proteins. Whole-exome sequencing was conducted to screen for potential pathogenic variants within the families. The SWISS-MODEL online platform was used to predict the three-dimensional structures of the mutant and wild-type proteins based on bioinformatics analysis. The predicted structures were then visualized using PyMOL software.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two known\n                      <jats:italic>MSH2<\/jats:italic>\n                      missense variants were identified: NM_000251.3:c.2633A&amp;gt;T:p.E878V in Family 1 and NM_000251.3:c.998G&amp;gt;A:p.C333Y in Family 2. A novel variant, designated as NM_000251.3:c.507del:p.Q170Rfs*4, was identified in the\n                      <jats:italic>MSH2<\/jats:italic>\n                      gene of Family 3. This variant is caused by the deletion of an adenine at nucleotide position 507 within the\n                      <jats:italic>MSH2<\/jats:italic>\n                      coding sequence, resulting in a frameshift. Consequently, glutamine at amino acid position 170 is altered to arginine, and a premature termination codon is introduced three residues downstream. This frameshift is predicted to generate a truncated protein of only 172 amino acids.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>MSH2<\/jats:italic>\n                      missense variant NM_000251.3:c.2633A&amp;gt;T:p.E878V was classified as a variant of uncertain significance regarding its role in LS. In contrast, the NM_000251.3:c.998G&amp;gt;A:p.C333Y missense variant was confirmed as pathogenic. Furthermore, the novel frameshift deletion NM_000251.3:c.507del:p.Q170Rfs*4 was also identified as a pathogenic variant.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1774595","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:34:01Z","timestamp":1774935241000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel frameshift variant in MSH2 (p.Q170Rfs4) associated with suspected Lynch syndrome in a Chinese family"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiawen","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Geriatric Outpatient, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pain, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichun","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengzhi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Physical Examination, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.7150\/ijbs.118896","article-title":"A SENP7-SIRT1-Il-10 axis driven by DeSUMOylation promotes breg differentiation and immune evasion in colorectal 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