{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T09:20:25Z","timestamp":1770456025427,"version":"3.49.0"},"reference-count":47,"publisher":"Georg Thieme Verlag KG","issue":"04","funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"crossref","award":["54\/28\/2012-HUM-BMS"],"award-info":[{"award-number":["54\/28\/2012-HUM-BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder\nwith a combined occurrence of tumours of parathyroid glands, pancreatic\nislets, and anterior pituitary. About 90% of these patients carry\nmutations in the MEN1 gene, though the spectrum is not well defined in\nIndia. Forty clinically suspected cases of MEN1 were enrolled prospectively\nover six years; 32 patients (23 index-cases and nine affected relatives)\nwith\u22652 classical endocrine tumours of MEN1 were considered definite,\nand eight were categorised as \u2018MEN1-like\u2019. Details of their\nclinical presentation, treatment and mutational analysis including MEN1\ngene, 3\u2032 and 5\u2032 untranslated regions (UTR) of MEN1, CDKN1B,\nand CaSR genes were collated. Asymptomatic first-degree relatives were also\nscreened. Among the 32 definite MEN1 patients, all had primary\nhyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic\nneuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the\n23 definite index-cases, 13 (56.5%) carried mutations in the MEN1\ngene. Five of nine affected first-degree relatives (55.5%), and four\nof 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of\n10 MEN1 mutation-negative definite index-cases harboured p.V109G\npolymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for\nmutations and large deletions in MEN1, mutations in 3\u2032 and\n5\u2032 UTR of MEN1, CaSR and CDKN1B genes. The study has helped to\nclearly document the pattern of mutations among Indian MEN1 patients.\nHowever, the absence of MEN1 mutation in ~44% of cases and\nthe presence of p.V109G polymorphism in CDKN1B gene raise the question\nwhether such polymorphisms could independently contribute to\npathogenesis.<\/jats:p>","DOI":"10.1055\/a-1402-0183","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T22:32:09Z","timestamp":1618439529000},"page":"245-256","source":"Crossref","is-referenced-by-count":6,"title":["Clinical Profile and Mutations Associated with Multiple Endocrine Neoplasia-Type1 (MEN1) and Their First-Degree Relatives at Risk of Developing MEN1: A Prospective Study"],"prefix":"10.1055","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9082-2387","authenticated-orcid":false,"given":"Asha Hesarghatta","family":"Shyamasunder","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7964-417X","authenticated-orcid":false,"given":"Rekha","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Christian Medical College, Vellore, Tamil\nNadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hemalatha","family":"Ramamoorthy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Christian Medical College, Vellore, Tamil\nNadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhananjayan","family":"Sakhti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Christian Medical College, Vellore, Tamil\nNadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie Therese","family":"Manipadam","sequence":"additional","affiliation":[{"name":"Department of Pathology, Christian Medical College, Vellore, Tamil\nNadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9520-2072","authenticated-orcid":false,"given":"Nitin","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas Vizhalil","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Jebasingh","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4614-9519","authenticated-orcid":false,"given":"Nihal","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak Thomas","family":"Abraham","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, Christian Medical College, Vellore,\nTamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mazhuvanchary Jacob","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, Christian Medical College, Vellore,\nTamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ari George","family":"Chacko","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Christian Medical College, Vellore, Tamil\nNadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Christian Medical College, Vellore, Tamil\nNadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Rajaratnam","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.5493\/wjem.v5.i2.124","article-title":"Genetic test in multiple endocrine neoplasia type 1 syndrome: An evolving\nstory","volume":"5","author":"F Marini","year":"2015","journal-title":"World J Exp Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1210\/jc.2012-1230","article-title":"Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)","volume":"97","author":"R V Thakker","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3389\/fendo.2019.00339","article-title":"Multiple Endocrine Neoplasia Type 1 (MEN1): An Update and the Significance of\nEarly Genetic and Clinical Diagnosis","volume":"10","author":"CD C Kamilaris","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1365-2265.1996.tb02069.x","article-title":"Prolactinoma presenting in identical twins with multiple endocrine neoplasia\ntype 1","volume":"45","author":"D E Flanagan","year":"1996","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"F1000 Faculty Rev","DOI":"10.12688\/f1000research.7230.1","article-title":"Genetics of multiple endocrine neoplasia type 1 syndrome: what's new and\nwhat's old","volume":"6","author":"A Falchetti","year":"2017","journal-title":"F1000 Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"E1089","DOI":"10.1002\/humu.21170","article-title":"Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine\nNeoplasia type1 (MEN1)","volume":"31","author":"J J Turner","year":"2010","journal-title":"Hum Mutat"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/humu.20605","article-title":"Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported\nin the first decade following identification of the gene","volume":"29","author":"M C Lemos","year":"2008","journal-title":"Hum Mutat"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3389\/fendo.2018.00533","article-title":"The Importance of an Early and Accurate MEN1 Diagnosis","volume":"9","author":"J M de Laat","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1210\/jc.2014-2700","article-title":"Acromegaly: an endocrine society clinical practice guideline","volume":"99","author":"L Katznelson","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1210\/jc.2009-2670","article-title":"A consensus on criteria for cure of acromegaly","volume":"95","author":"A Giustina","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1210\/jc.2008-0125","article-title":"The diagnosis of Cushing's syndrome: an Endocrine Society Clinical\nPractice Guideline","volume":"93","author":"L K Nieman","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1210\/jc.2015-1818","article-title":"Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice\nGuideline","volume":"100","author":"L K Nieman","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ando.2015.04.002","article-title":"Management of clinically non-functioning pituitary adenoma","volume":"76","author":"P Chanson","year":"2015","journal-title":"Ann Endocrinol (Paris)"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1210\/jc.2010-1692","article-title":"Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical\npractice guideline","volume":"96","author":"S Melmed","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1210\/jc.2008-1410","article-title":"Evaluation and management of adult hypoglycemic disorders: an Endocrine Society\nClinical Practice Guideline","volume":"94","author":"P E Cryer","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1002\/bjs.5987","article-title":"Management of sporadic and multiple endocrine neoplasia type 1 gastrinomas","volume":"94","author":"V Fendrich","year":"2007","journal-title":"Br J Surg"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1097\/SLA.0000000000002191","article-title":"Long-term Follow-up of MEN1 Patients Who Do Not Have Initial Surgery for Small\n\u22642 cm Nonfunctioning Pancreatic Neuroendocrine Tumors, an AFCE and GTE\nStudy: Association Francophone de Chirurgie Endocrinienne & Groupe\nd'Etude des Tumeurs Endocrines","volume":"268","author":"F Triponez","year":"2018","journal-title":"Ann Surg"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1677\/ERC-10-0028","article-title":"MEN1 in pancreatic endocrine tumors: analysis of gene and protein status in 169\nsporadic neoplasms reveals alterations in the vast majority of cases","volume":"17","author":"V Corbo","year":"2010","journal-title":"Endocr Relat Cancer"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1530\/ERC-11-0362","article-title":"Cyclin-dependent kinase inhibitor 1B (CDKN1B) gene variants in AIP\nmutation-negative familial isolated pituitary adenoma kindreds","volume":"19","author":"M A Tichomirowa","year":"2012","journal-title":"Endocr Relat Cancer"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.3748\/wjg.14.4486","article-title":"Association between calcium sensing receptor gene polymorphisms and chronic\npancreatitis in a US population: role of serine protease inhibitor Kazal 1type\nand alcohol","volume":"14","author":"V Muddana","year":"2008","journal-title":"World J Gastroenterol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1001\/archderm.1997.03890430067009","article-title":"Multiple facial angiofibromas and collagenomas in patients with Multiple\nendocrine neoplasia type 1","volume":"133","author":"T N Darling","year":"1997","journal-title":"Arch Dermatol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"558","DOI":"10.3389\/fendo.2018.00558","article-title":"Total and Subtotal parathyroidectomy in young patients with Multiple endocrine\nneoplasia type 1- related primary hyperparathyroidism: Potential post-surgical\nbenefits and complications","volume":"9","author":"F Tonelli","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/j.1365-2265.2011.04227.x","article-title":"Multiple endocrine neoplasia type 1 in Japan: establishment and analysis of a\nmulticentre database","volume":"76","author":"A Sakurai","year":"2012","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1086\/301953","article-title":"Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1\nand related disorders","volume":"63","author":"S Giraud","year":"1998","journal-title":"Am J Hum Genet"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1136\/jmg.2003.017319","article-title":"A report of a national mutation testing service for the MEN1 gene: clinical\npresentations and implications for mutation testing","volume":"42","author":"J W Cardinal","year":"2005","journal-title":"J Med Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1210\/jc.2007-0476","article-title":"Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200\nunrelated cases","volume":"92","author":"E Tham","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s10689-016-9891-7","article-title":"Multiple endocrine neoplasia type 1 syndrome: single centre experience from\nwestern India","volume":"15","author":"M Goroshi","year":"2016","journal-title":"Fam Cancer"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1097\/SLA.0b013e31824c5145","article-title":"Primary hyperparathyroidism in MEN1 patients: a cohort study with longterm\nfollow-up on preferred surgical procedure and the relation with genotype","volume":"255","author":"C R Pieterman","year":"2012","journal-title":"Ann Surg"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"131","DOI":"10.6061\/clinics\/2012(Sup01)22","article-title":"Total parathyroidectomy in a large cohort of cases with hyperparathyroidism\nassociated with multiple endocrine neoplasia type 1: experience from a single\nacademic center","volume":"67","author":"F L Montenegro","year":"2012","journal-title":"Clinics (Sao Paulo)"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1097\/PAS.0b013e31815ade45","article-title":"Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome\n(MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1\npatients","volume":"32","author":"J Trouillas","year":"2008","journal-title":"Am J Surg Pathol"},{"key":"ref31","first-page":"4673","article-title":"Surgical management of Zollinger-Ellison syndrome: Classical considerations and\ncurrent controversies","volume":"25","author":"Q Q Shao","year":"2019","journal-title":"World J Gastroenterol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.surg.2016.09.017","article-title":"Operation for insulinomas in multiple endocrine neoplasia type 1: When\npancreatoduodenectomy is appropriate","volume":"161","author":"F Tonelli","year":"2017","journal-title":"Surgery"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1111\/cen.14094","article-title":"What is the appropriate management of nonfunctioning pancreatic neuroendocrine\ntumours disclosed on screening in adult patients with multiple endocrine\nneoplasia type 1?","volume":"91","author":"B G Challis","year":"2019","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/s12020-015-0702-y","article-title":"Role of (68)Ga-DOTATATE PET\/CT in patients with multiple endocrine\nneoplasia type 1 (MEN1)","volume":"52","author":"S Lastoria","year":"2016","journal-title":"Endocrine"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1365-2265.2005.02190.x","article-title":"Detection of an MEN1 gene mutation depends on clinical features and supports\ncurrent referral criteria for diagnostic molecular genetic testing","volume":"62","author":"S Ellard","year":"2005","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.mce.2006.02.008","article-title":"Characteristics of the Danish families with multiple endocrine neoplasia type\n1","volume":"249","author":"A C J\u00e4ger","year":"2006","journal-title":"Mol Cell Endocrinol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1530\/EJE-19-0522","article-title":"Whole genome sequencing of apparently mutation-negative MEN1 patients","volume":"182","author":"S Backman","year":"2020","journal-title":"Eur J Endocrinol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1097\/GIM.0b013e3181be5c97","article-title":"Multiple endocrine neoplasia type 1 (MEN1): not only inherited endocrine\ntumors","volume":"11","author":"A Falchetti","year":"2009","journal-title":"Genet Med"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12916-016-0708-1","article-title":"MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative\npatients","volume":"14","author":"J M de Laat","year":"2016","journal-title":"BMC Med"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3410\/M2-14","article-title":"Genetic screening for multiple endocrine neoplasia syndrome type 1 (MEN-1): when\nand how","volume":"2","author":"A Falchetti","year":"2010","journal-title":"F1000 Med Rep"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s13023-018-0938-8","article-title":"Multiple endocrine neoplasia type 1: extensive analysis of a large database of\nFlorentine patients","volume":"13","author":"F Marini","year":"2018","journal-title":"Orphanet J Rare Dis"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1210\/jc.2008-2083","article-title":"Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple\nendocrine neoplasia type 1 and related states [published correction\nappearead in]","volume":"94","author":"S K Agarwal","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1530\/EJE-14-0130","article-title":"Association between the p27 rs2066827 variant and tumor multiplicity in patients\nharboring MEN1 germline mutations","volume":"171","author":"V C Longuini","year":"2014","journal-title":"Eur J Endocrinol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1111\/jcmm.12552","article-title":"Prognostic role of the CDNK1B V109G polymorphism in multiple endocrine neoplasia\ntype 1","volume":"19","author":"L Circelli","year":"2015","journal-title":"J Cell Mol Med"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1089\/cbr.2012.1229","article-title":"p27(Kip1) V109G polymorphism and cancer risk: a systematic review and\nmeta-analysis","volume":"27","author":"F Wei","year":"2012","journal-title":"Cancer Biother Radiopharm"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1530\/EJE-18-0430","article-title":"Germline mutation landscape of multiple endocrine neoplasia type 1 using full\ngene next-generation sequencing","volume":"179","author":"R A Carvalho","year":"2018","journal-title":"Eur J Endocrinol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1210\/jcem.87.6.8607","article-title":"Frequent occurrence of an intron 4 mutation in multiple endocrine neoplasia type\n1","volume":"87","author":"J J Turner","year":"2002","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1402-0183.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T22:36:26Z","timestamp":1618439786000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1402-0183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4]]},"references-count":47,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2021,4,14]]},"published-print":{"date-parts":[[2021,4]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1402-0183","relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4]]}}}