{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:35:34Z","timestamp":1789788934028,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T00:00:00Z","timestamp":1570579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["CONICYT-FONDAP 15130011"],"award-info":[{"award-number":["CONICYT-FONDAP 15130011"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009610","name":"Pontificia Universidad Cat\u00f3lica de Chile","doi-asserted-by":"publisher","award":["UC IC 07\/15"],"award-info":[{"award-number":["UC IC 07\/15"]}],"id":[{"id":"10.13039\/501100009610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"publisher","award":["17\/610"],"award-info":[{"award-number":["17\/610"]}],"id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1191928"],"award-info":[{"award-number":["1191928"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Germline pathogenic variants in the CDH1 gene are a well-established cause of hereditary diffuse gastric cancer (HDGC) syndrome. The aim of this study was to characterize CDH1 mutations associated with HDGC from Chile, a country with one of the highest incidence and mortality rates in the world for gastric cancer (GC). Here, we prospectively include probands with family history\/early onset of diffuse-type of GC. The whole coding sequence of the CDH1 gene was sequenced from genomic DNA in all patients, and a multidisciplinary team managed each family member with a pathogenic sequence variant. Thirty-six cases were included (median age 44 years\/male 50%). Twenty-seven (75%) patients had diffuse-type GC at \u226450 years of age and 19 (53%) had first or second-degree family members with a history of HDGC. Two cases (5.5%) carried a non-synonymous germline sequence variant in the CDH1 gene: (a) The c.88C&gt;A missense variant was found in a family with three diffuse-type GC cases; and (b) c.1531C&gt;T a nonsense pathogenic variant was identified in a 22-year-old proband with no previous family history of HDGC. Of note, six family members carry the same nonsense pathogenic variant. Prophylactic gastrectomy in the proband\u2019s sister revealed stage I signet-ring cell carcinoma. The finding of 1531C&gt;T pathogenic variant in the CDH1 in proband with no previous family history of HDGC warrants further study to uncover familial clustering of disease in CDH1 negative patients. This finding may be particularly relevant in high incidence countries, such as the case in this report.<\/jats:p>","DOI":"10.3390\/ijms20204980","type":"journal-article","created":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T11:25:57Z","timestamp":1570620357000},"page":"4980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Identification of c.1531C&gt;T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6262-4930","authenticated-orcid":false,"given":"Enrique","family":"Norero","sequence":"first","affiliation":[{"name":"Esophagogastric Surgery Unit, Surgery Department, Hospital Dr. Sotero del Rio, Santiago 8207257, Chile"},{"name":"Digestive Surgery Department, Hospital Clinico Universidad Cat\u00f3lica de Chile, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5133-1964","authenticated-orcid":false,"given":"M. Alejandra","family":"Alarcon","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5007-2684","authenticated-orcid":false,"given":"Christopher","family":"Hakkaart","sequence":"additional","affiliation":[{"name":"Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"de Mayo","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"},{"name":"Faculty of Sciences, School of Medicine Universidad Mayor Santiago Chile, Santiago 8580745, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Mellado","sequence":"additional","affiliation":[{"name":"Genetic Unit, Pediatrics Division, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-8986","authenticated-orcid":false,"given":"Marcelo","family":"Garrido","sequence":"additional","affiliation":[{"name":"Hematology and Oncology Department, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Aguayo","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Dr. Sotero del Rio, Santiago 8207257, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Lagos","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javiera","family":"Torres","sequence":"additional","affiliation":[{"name":"Pathology Department, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Calvo","sequence":"additional","affiliation":[{"name":"Esophagogastric Surgery Unit, Surgery Department, Hospital Dr. Sotero del Rio, Santiago 8207257, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parry","family":"Guilford","sequence":"additional","affiliation":[{"name":"Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro H.","family":"Corvalan","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"},{"name":"Hematology and Oncology Department, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/ijc.31937","article-title":"Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods","volume":"144","author":"Ferlay","year":"2019","journal-title":"Int. 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