{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:56:49Z","timestamp":1780405009285,"version":"3.54.1"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Johann Wolfgang Goethe-Universit\u00e4t, Frankfurt am Main"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Endocr Disord"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>MEN1 mutations can inactivate or disrupt menin function and are leading to multiple endocrine neoplasia type 1, a rare heritable tumor syndrome. <\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We report on a MEN1 family with a novel heterozygous germline mutation, c.674delG; p.Gly225Aspfs*56 in exon 4 of the MEN1 gene. Diagnosis and clinical phenotyping of MEN1 was established by laboratory tests, ultrasound, biopsy, MRI imaging and endosonography. The clinical course of the disease was followed in the index patient and her family members for eight years. The mutation was associated with distinct clinical phenotypes in the index patient and three family members harboring p.Gly225Aspfs*56. Family members affected showed primary hyperparathyroidism but variable patterns of associated endocrine tumors, adrenal cortical adenomas, prolactinoma, multifocal pancreatic neuroendocrine tumors, insulinoma and nonsecretory neuroendocrine tumors of the pancreas. The mutation c.674delG; p.Gly225Aspfs*56 leads to a frameshift from codon 225 with early truncation of the menin protein. In silico analysis predicts loss of multiple protein-menin interactions in p.Gly225Aspfs*56, potentially rendering menin insufficient to control cell division and replication. However, no aggressive neuroendocrine tumors were observed in the follow-up of this family.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We report a novel heterozygous MEN1 frameshift mutation, potentially causing (at least partial) inactivation of menin tumor suppression potential but lacking a genotype\u2013phenotype correlation. Our study highlights the importance of personalized care with appropriate testing and counseling in MEN1 families.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12902-022-00978-9","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T11:03:01Z","timestamp":1647255781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-4863","authenticated-orcid":false,"given":"Christoph","family":"Welsch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Katharina","family":"Fl\u00fcgel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Rondot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egbert","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishani","family":"Sircar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Nu\u00dfbaumer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Bojunga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"issue":"9","key":"978_CR1","doi-asserted-by":"publisher","first-page":"2990","DOI":"10.1210\/jc.2012-1230","volume":"97","author":"RV Thakker","year":"2012","unstructured":"RV Thakker PJ Newey GV Walls J Bilezikian H Dralle PR Ebeling S Melmed A Sakurai F Tonelli ML Brandi 2012 Endocrine Society Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1) J Clin Endocrinol Metab 97 9 2990 3011","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"978_CR2","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1093\/qjmed\/89.9.653","volume":"89","author":"D Trump","year":"1996","unstructured":"D Trump B Farren C Wooding JT Pang GM Besser KD Buchanan CR Edwards DA Heath CE Jackson S Jansen K Lips JP Monson D O'Halloran J Sampson SM Shalet MH Wheeler A Zink RV Thakker 1996 Clinical studies of multiple endocrine neoplasia type 1 (MEN1) QJM 89 9 653 669","journal-title":"QJM"},{"issue":"7","key":"978_CR3","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/hmg\/6.7.1177","volume":"6","author":"I Lemmens","year":"1997","unstructured":"I Lemmens WJ Van de Ven K Kas CX Zhang S Giraud V Wautot N Buisson K De Witte J Salandre G Lenoir M Pugeat A Calender F Parente D Quincey P Gaudray MJ De Wit CJ Lips JW H\u00f6ppener S Khodaei AL,Grant G Weber S Kyt\u00f6l\u00e4 BT Teh F Farnebo RV Thakker  1997 Identification of the multiple endocrine neoplasia type 1 (MEN1) gene The European Consortium on MEN1 Hum Mol Genet 6 7 1177 83","journal-title":"Hum Mol Genet"},{"issue":"5311","key":"978_CR4","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1126\/science.276.5311.404","volume":"276","author":"SC Chandrasekharappa","year":"1997","unstructured":"SC Chandrasekharappa SC Guru P Manickam SE Olufemi FS Collins MR Emmert-Buck LV Debelenko Z Zhuang IA Lubensky LA Liotta JS Crabtree Y Wang BA Roe J Weisemann MS Boguski SK Agarwal MB Kester YS Kim C Heppner Q Dong AM Spiegel AL Burns SJ Marx 1997 Positional cloning of the gene for multiple endocrine neoplasia-type 1 Science 276 5311 404 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JunD-mediated transcriptional activity by association with an mSin3A-histone deacetylase complex Cancer Res 63 19 6135 6139","journal-title":"Cancer Res"},{"issue":"11","key":"978_CR15","doi-asserted-by":"publisher","first-page":"5282","DOI":"10.1210\/jcem.86.11.8011","volume":"86","author":"F Gibril","year":"2001","unstructured":"F Gibril DJ Venzon JV Ojeaburu S Bashir RT Jensen 2001 Prospective study of the natural history of gastrinoma in patients with MEN1: definition of an aggressive and a nonaggressive form J Clin Endocrinol Metab 86 11 5282 5293","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"978_CR16","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1091\/mbc.e13-02-0110","volume":"25","author":"G Huot","year":"2014","unstructured":"G Huot M Vernier V Bourdeau L Doucet E Saint-Germain MF Gaumont-Leclerc A Moro G Ferbeyre 2014 CHES1\/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis Mol Biol Cell 25 5 554 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September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval N\/A and informed consent to participate to the study was obtained from the index patient and her family members.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent was obtained from the patient and her family members in written form. A copy of the consent form is available for review by the Editor of this journal upon request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"64"}}