{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T16:14:26Z","timestamp":1783354466895,"version":"3.54.6"},"reference-count":15,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Objective.<\/jats:bold>\n                    Multiple endocrine neoplasia type 1 (MEN1) is a very rare genetic disorder characterized by an autosomal dominant inheritance. We aim through this case series to delineate the wide spectrum of its clinical features.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods.<\/jats:bold>\n                    In the present study, we report the clinical and genetic findings of four siblings affected by this disorder. DNA was extracted from patients\u2019 blood leukocytes using a phenol-chloroform method and assessed for purity with a NanoDrop spectrophotometer. Ten exons of the\n                    <jats:italic>MEN1<\/jats:italic>\n                    gene were amplified by PCR, verified by gel electrophoresis, and sequenced using Big Dye Terminator chemistry followed by capillary electrophoresis. The sequences were than analyzed with CHROMAS and compared to reference sequences. As for the variant, interpretation and pathogenicity were assessed using Ensembl, ClinVar, dbSNP, gnomAD, Alamut Visual, and VARSOME.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results.<\/jats:bold>\n                    We highlight the wide range of phenotypes encompassing primary hyperparathyroidism, macroprolactinoma, lipomas, papillary thyroid carcinoma, ectopic thyroid, multinodular goiter, and bilateral adrenal nodules observed in this family contrasting with the same pathogenic frameshift mutation. We also pinpoint to a second mutation detected in two of the siblings while discussing its pathogenicity. Finally, we provide an overview of the clinical manifestations of MEN1 and its genetic background.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion.<\/jats:bold>\n                    This research sets the stage to further investigate the molecular mechanisms underlying the novel nonsense mutation. Additionally, it incites other research to explore the frequency of this mutation in other populations and finally to conduct functional studies.\n                  <\/jats:p>","DOI":"10.2478\/enr-2026-0004","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:06:05Z","timestamp":1774940765000},"page":"29-36","source":"Crossref","is-referenced-by-count":0,"title":["One genotype with a myriad of phenotypes: A family with multiple endocrine neoplasia"],"prefix":"10.2478","volume":"60","author":[{"given":"Oumeyma","family":"Trimeche","sequence":"first","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Mnif","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Abdelhedi","sequence":"additional","affiliation":[{"name":"2 Genetics Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaouther El","family":"Arbi","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosra","family":"Lajmi","sequence":"additional","affiliation":[{"name":"2 Genetics Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Charfi","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouna","family":"Mnif","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faten Hadj","family":"Kacem","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhouha Ben","family":"Salah","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khouloud","family":"Boujelbene","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Abid","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouna","family":"Elleuch","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nebila","family":"Rekik","sequence":"additional","affiliation":[{"name":"1 Endocrinology Department , Hedi Chaker University Hospital , Sfax , Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"2026070615003163598_j_enr-2026-0004_ref_001","doi-asserted-by":"crossref","unstructured":"Al-Salameh A, Cadiot G, Calender A, Goudet P, Chanson P. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol 17, 207\u2013224, 2021.","DOI":"10.1038\/s41574-021-00468-3"},{"key":"2026070615003163598_j_enr-2026-0004_ref_002","doi-asserted-by":"crossref","unstructured":"Desai D, McPherson LA, Higgins JP, Weigel RJ. Genetic analysis of a papillary thyroid carcinoma in a patient with MEN1. Ann Surg Oncol 8, 342\u2013346, 2001.","DOI":"10.1007\/s10434-001-0342-8"},{"key":"2026070615003163598_j_enr-2026-0004_ref_003","doi-asserted-by":"crossref","unstructured":"Eller-Vainicher C, Chiodini I, Battista C, Viti R, Mascia ML, Massironi S, Peracchi M, D\u2019Agruma L, Minisola S, Corbetta S, Cole DEC, Spada A, Scillitani A. Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity. J Bone Miner Res 24, 1404\u20131410, 2009.","DOI":"10.1359\/jbmr.090304"},{"key":"2026070615003163598_j_enr-2026-0004_ref_004","doi-asserted-by":"crossref","unstructured":"Falchetti A. Genetics of multiple endocrine neoplasia type 1 syndrome: what\u2019s new and what\u2019s old. F1000Research 6, F1000 Faculty Rev\u201373, 2017.","DOI":"10.12688\/f1000research.7230.1"},{"key":"2026070615003163598_j_enr-2026-0004_ref_005","doi-asserted-by":"crossref","unstructured":"Kamilaris CDC, Stratakis CA. Multiple endocrine neoplasia type 1 (MEN1): an update and the significance of early genetic and clinical diagnosis. Front Endocrinol 10, 339, 2019.","DOI":"10.3389\/fendo.2019.00339"},{"key":"2026070615003163598_j_enr-2026-0004_ref_006","unstructured":"Kim HJ, Park JS, Kim CS, Kang ES, Cha BS, Lim SK, Kim KR, Lee HC, Ahn CW. A case of multiple endocrine neoplasia type 1 combined with papillary thyroid carcinoma. Yonsei Med J 49, 503\u2013506, 2008."},{"key":"2026070615003163598_j_enr-2026-0004_ref_007","unstructured":"Kytola S, Villablanca A, Ebeling T, Nord B, Larsson C, Hoog A, Wong FK, Valimaki M, Vierimaa O, Teh BT, Salmela PI, Leisti J. Founder effect in multiple endocrine neoplasia type 1 (MEN 1) in Finland. J Med Genet 38, 185\u2013189, 2001."},{"key":"2026070615003163598_j_enr-2026-0004_ref_008","doi-asserted-by":"crossref","unstructured":"Liu Q, Wu L, Zheng X, Ma C, Na R, Qiu L, Liu Z, Liao L. Multiple endocrine neoplasia type 1 with ectopic parathyroid adenoma. Arch Med Sci 18, 829\u2013832, 2022.","DOI":"10.5114\/aoms\/147737"},{"key":"2026070615003163598_j_enr-2026-0004_ref_009","unstructured":"Marx SJ, Agarwal SK, Kester MB, Heppner C, Kim YS, Emmert-Buck MR, Debelenko LV, Lubensky IA, Zhuang Z, Guru SC, Manickam P, Olufemi SE, Skarulis MC, Doppman JL, Alexander RH, Liotta LA, Collins FS, Chandrasekharappa SC, Spiegel AM, Burns AL. Germline and somatic mutation of the gene for multiple endocrine neoplasia type 1 (MEN1). J Intern Med 243, 447\u2013453, 1998."},{"key":"2026070615003163598_j_enr-2026-0004_ref_010","doi-asserted-by":"crossref","unstructured":"Mele C, Mencarelli M, Caputo M, Mai S, Pagano L, Aimaretti G, Scacchi M, Falchetti A, Marzullo P. Phenotypes associated with MEN1 syndrome: a focus on genotype-phenotype correlations. Front Endocrinol 11, 591501, 2020.","DOI":"10.3389\/fendo.2020.591501"},{"key":"2026070615003163598_j_enr-2026-0004_ref_011","doi-asserted-by":"crossref","unstructured":"Perakakis N, Flohr F, Kayser G, Thomusch O, Parsons L, Billmann F, von Dobschuetz E, Rondot S, Seufert J, Laubner K. Multiple endocrine neoplasia type 1 associated with a new germline Men1 mutation in a family with atypical tumor phenotype. Hormones (Athens)15, 113\u2013117, 2016.","DOI":"10.1007\/BF03401410"},{"key":"2026070615003163598_j_enr-2026-0004_ref_012","doi-asserted-by":"crossref","unstructured":"Pieterman CRC, van Hulsteijn LT, den Heijer M, van der Luijt RB, Bonenkamp JJ, Hermus ARMM, Rinkes IHMB, Vriens MR, Valk GD, DutchMEN1 study group. Primary hyperparathyroidism in MEN1 patients: a cohort study with longterm follow-up on preferred surgical procedure and the relation with genotype. Ann Surg 255, 1171\u20131178, 2012.","DOI":"10.1097\/SLA.0b013e31824c5145"},{"key":"2026070615003163598_j_enr-2026-0004_ref_013","doi-asserted-by":"crossref","unstructured":"Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML, Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 97, 2990\u20133011, 2012.","DOI":"10.1210\/jc.2012-1230"},{"key":"2026070615003163598_j_enr-2026-0004_ref_014","doi-asserted-by":"crossref","unstructured":"Wautot V, Vercherat C, Lespinasse J, Chambe B, Lenoir GM, Zhang CX, Porchet N, Cordier M, Beroud C, Calender A. Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein. Hum Mutat 20, 35\u201347, 2002.","DOI":"10.1002\/humu.10092"},{"key":"2026070615003163598_j_enr-2026-0004_ref_015","doi-asserted-by":"crossref","unstructured":"Xu JL, Dong S, Sun LL, Zhu JX, Liu J. exon. World J Clin Cases 10, 1032\u20131040, 2022.","DOI":"10.12998\/wjcc.v10.i3.1032"}],"container-title":["Endocrine Regulations"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/reference-global.com\/pdf\/10.2478\/enr-2026-0004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:18:48Z","timestamp":1783351128000},"score":1,"resource":{"primary":{"URL":"https:\/\/reference-global.com\/article\/10.2478\/enr-2026-0004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":15,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3,24]]},"published-print":{"date-parts":[[2026,1,1]]}},"alternative-id":["10.2478\/enr-2026-0004"],"URL":"https:\/\/doi.org\/10.2478\/enr-2026-0004","relation":{},"ISSN":["1336-0329"],"issn-type":[{"value":"1336-0329","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]}}}