{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:52:11Z","timestamp":1791615131229,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T00:00:00Z","timestamp":1556236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/71397\/2010"],"award-info":[{"award-number":["SFRH\/BD\/71397\/2010"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/113014\/2015"],"award-info":[{"award-number":["SFRH\/BPD\/113014\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mutational spectrum of the MMR genes is highly heterogeneous, but specific mutations are observed at high frequencies in well\u2010defined populations or ethnic groups, due to founder effects. The <jats:italic>MSH2<\/jats:italic> mutation c.2152C&gt;T, p.(Gln718*), has occasionally been described in Lynch families worldwide, including in Portuguese Lynch syndrome families. During genetic testing for Lynch syndrome at the Portuguese Oncology Institutes of Porto and Lisbon, this mutation was identified in 28 seemingly unrelated families. In order to evaluate if this alteration is a founder mutation, haplotype analysis using microsatellite and SNP markers flanking the <jats:italic>MSH2<\/jats:italic> gene was performed in the 28 probands and 87 family members. Additionally, the geographic origin of these families was evaluated and the age of the mutation estimated. Twelve different haplotypes were phased for 13 out of the 28 families and shared a conserved region of \u223c3.6\u2009Mb. Based on the mutation and recombination events observed in the microsatellite haplotypes and assuming a generation time of 25\u2009years, the age estimate for the <jats:italic>MSH2<\/jats:italic> mutation was 273\u2009\u00b1\u200964\u2009years. The geographic origins of these families were mostly from the Northern region of Portugal. Concluding, these results suggest that the <jats:italic>MSH2<\/jats:italic> c.2152C&gt;T alteration is a founder mutation in Portugal with a relatively recent origin. Furthermore, its high proportion indicates that screening for this mutation as a first step, together with the previously reported Portuguese founder mutations, may be cost\u2010effective in genetic testing of Lynch syndrome suspects of Portuguese ancestry.<\/jats:p>","DOI":"10.1002\/gcc.22759","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T06:52:50Z","timestamp":1554879170000},"page":"657-664","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The nonsense mutation <i>MSH2<\/i> c.2152C&gt;T shows a founder effect in Portuguese Lynch syndrome families"],"prefix":"10.1002","volume":"58","author":[{"given":"Manuela","family":"Pinheiro","sequence":"first","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Francisco","sequence":"additional","affiliation":[{"name":"Molecular Pathobiology Research Unit Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Veiga","sequence":"additional","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Filipe","sequence":"additional","affiliation":[{"name":"Molecular Pathobiology Research Unit Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Maia","sequence":"additional","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Claro","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Portuguese Oncology Institute of Lisbon  Lisbon Portugal"},{"name":"Familial Risk Clinic Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Lage","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Portuguese Oncology Institute of Lisbon  Lisbon Portugal"},{"name":"Familial Risk Clinic Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Lopes","sequence":"additional","affiliation":[{"name":"Department of Pathology Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Portuguese Oncology Institute of Lisbon  Lisbon Portugal"},{"name":"Familial Risk Clinic Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Portuguese Oncology Institute of Lisbon  Lisbon Portugal"},{"name":"Familial Risk Clinic Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Department of Pathology Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Familial Risk Clinic Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Department of Pathology Portuguese Oncology Institute of Porto  Porto Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS) University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Chaves","sequence":"additional","affiliation":[{"name":"Department of Pathology Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f3nio Dias","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Portuguese Oncology Institute of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Molecular Pathobiology Research Unit Portuguese Oncology Institute of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4896-5982","authenticated-orcid":false,"given":"Manuel R.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Genetics Portuguese Oncology Institute of Porto  Porto Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS) University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.17.5950"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra012242"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djk051"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.09.003"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.283"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70510-X"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1278"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-004-1447-6"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.048991"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181cd666c"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.13088"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2016.0108"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204376"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/373963"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.013714"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.030999"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31821dd525"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12062"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.124"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20320"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-015-9832-x"},{"key":"e_1_2_6_23_1","first-page":"5248","article-title":"A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer","volume":"58","author":"Boland CR","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.02.009"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-012-9550-6"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.4.297"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-587"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1086\/302612"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.1.94"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-134"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6599"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.10.1502"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694supp-246"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<116::AID-HUMU24>3.0.CO;2-Q"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32537"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.5704"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.743"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-011-9461-y"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-12-64"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139753"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70041-5"},{"key":"e_1_2_6_42_1","first-page":"271","article-title":"Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study","volume":"58","author":"Neuhausen SL","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_43_1","first-page":"526","article-title":"Joint Bayesian estimation of mutation location and age using linkage disequilibrium","volume":"8","author":"Rannala B","year":"2003","journal-title":"Pac Symp Biocomput"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-169"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1353\/hub.2005.0002"},{"key":"e_1_2_6_46_1","first-page":"259","article-title":"Migra\u00e7\u00f5es internas e de m\u00e9dia dist\u00e2ncia em Portugal de 1500 a 1900","volume":"1","author":"Oliveira O","year":"1995","journal-title":"ARQUIP\u00c9LAGO Hist\u00f3ria"},{"key":"e_1_2_6_47_1","first-page":"95","article-title":"Deslocamentos da popula\u00e7\u00e3o em Portugal. Programa de um estudo","volume":"85","author":"Ribeiro O","year":"2008","journal-title":"Finisterra"},{"key":"e_1_2_6_48_1","unstructured":"SousaF MartinsI PereiraC.A emigra\u00e7\u00e3o Portuguesa para o Brasil. N.\u00b0 edi\u00e7\u00e3o: 1117. Porto Portugal: Coedi\u00e7\u00e3o CEPESE \u2013 Centro de Estudos da Popula\u00e7\u00e3o Economia e Sociedade\/Edi\u00e7\u00f5es Afrontamento;2007."},{"key":"e_1_2_6_49_1","unstructured":"ArrudaJ FerliniV MatosM SousaF.De colonos a imigrantes: i(E)migra\u00e7\u00e3o portuguesa para o Brasil. S\u00e3o Paulo Brasil: Editora Alameda;2013."},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12441"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.22759","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22759","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gcc.22759","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22759","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T17:19:32Z","timestamp":1694279972000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.22759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,26]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1002\/gcc.22759"],"URL":"https:\/\/doi.org\/10.1002\/gcc.22759","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,26]]},"assertion":[{"value":"2019-02-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}