{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T06:38:49Z","timestamp":1778567929848,"version":"3.51.4"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010804","name":"Faculty of Medicine, Prince of Songkla University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Familial adenomatous polyposis (FAP) is caused by pathogenic germline variants in the <jats:italic>APC<\/jats:italic> gene. To date, multiple pathogenic variants in coding regions, splice sites, and deep intronic regions have been revealed. However, there are still pathogenic variants that remain unidentified.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Twenty-nine primer pairs flanking exons 2\u201316 (i.e., coding exons 1\u201315) of <jats:italic>APC<\/jats:italic> and their exon\u2013intron junctions were used for germline pathogenic variant screening in Southern Thai patients with familial adenomatous polyposis (FAP). Transcription analysis was performed to confirm the pathogenicity of a splice site deletion of intron 10. Family members were interviewed for clinical histories. Blood samples were collected from 18 family members for a segregation study. Subsequently, clinical data of affected members were collected from the hospital databases.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found a distinct heterozygous 16-bp deletion at the splice donor site of intron 10 leading to a skipping of exon 10 which was confirmed by transcript analysis (<jats:italic>APC<\/jats:italic>: c 1312\u2009+\u20094_1312\u2009+\u200919del, r.934_1312del). Predictive testing for the pathogenic <jats:italic>APC<\/jats:italic> variant in 18 of the proband\u2019s family members (ten healthy and eight affected) from three generations showed the same heterozygous germline pathogenic variant in eight affected adult members (15\u201362\u00a0years old) and two children (7 and 10\u00a0years old). Seven of the ten carriers of the disease-causing variant had undergone colonoscopy, and colonic polyps were found in all cases, which confirmed the segregation of the inherited pathogenic variant. The phenotypic spectrum was found to vary within the family; and some affected family members exhibited extracolonic manifestations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>To our knowledge, the pathogenic <jats:italic>APC<\/jats:italic> variant, c.1312\u2009+\u20094_1312\u2009+\u200919del, r.934_1312del, has not previously been reported. This study is one of the few reports describing the phenotypic consequences of a pathogenic <jats:italic>APC<\/jats:italic> variant in a high number of affected family members.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-021-00933-y","type":"journal-article","created":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T15:05:48Z","timestamp":1616166348000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A distinct APC pathogenic germline variant identified in a southern Thai family with familial adenomatous polyposis"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-7756","authenticated-orcid":false,"given":"Worrawit","family":"Wanitsuwan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-3640","authenticated-orcid":false,"given":"Sukanya","family":"Vijasika","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0584-5101","authenticated-orcid":false,"given":"Pichai","family":"Jirarattanasopa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5353-0409","authenticated-orcid":false,"given":"Sukanya","family":"Horpaopan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"933_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13053-017-0065-x","volume":"15","author":"BA Talseth-Palmer","year":"2017","unstructured":"Talseth-Palmer BA. The genetic basis of colonic adenomatous polyposis syndromes. Hereditary Cancer Clin Pract. 2017;15:5.","journal-title":"Hereditary Cancer Clin Pract"},{"issue":"6","key":"933_CR2","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1016\/0016-5085(91)90666-9","volume":"100","author":"GM Petersen","year":"1991","unstructured":"Petersen GM, Slack J, Nakamura Y. Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology. 1991;100(6):1658\u201364.","journal-title":"Gastroenterology"},{"issue":"5","key":"933_CR3","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1136\/gut.2007.136127","volume":"57","author":"HF Vasen","year":"2008","unstructured":"Vasen HF, Moslein G, Alonso A, Aretz S, Bernstein I, Bertario L, Blanco I, Bulow S, Burn J, Capella G, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). 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Written informed consents were obtained from all participants and the parents of the minor participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consents for publication of identifying images and personal or clinical details were obtained from participants who were included in Table , and from the parents of participants under the age of 18. In addition, the written informed consents for publication of identifying images and personal or clinical details of other participants who were presented in the study (Fig.\u00a0) were obtained from their relative.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"87"}}