{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:28:34Z","timestamp":1786649314548,"version":"build-2736575974"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>Limited data exist on the genetic profile of Familial primary hyperparathyroidism (FPHPT) in the Indian population. This study was conducted to determine the prevalence of targeted gene mutations in high-risk patients with PHPT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      This prospective cross-sectional study was conducted in the Department of Endocrinology at our University Hospital from February 2021 to February 2023, in which 103 patients diagnosed with PHPT were taken. A customised gene panel (\n                      <jats:italic toggle=\"yes\">MEN1, RET, CDKNIB<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">CDC73<\/jats:italic>\n                      ) using next-generation sequencing (NGS) was performed in 39 patients with a strong suspicion of FPHPT based on age &lt;35 years, family history of PHPT, multiglandular disease, hyperparathyroidism jaw tumour, cystic parathyroid adenoma (PA), parathyroid carcinoma (PC) and suspicion of MEN 1\/2A\/4 syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Germline variants were observed in 11\/39 (28.2%).\n                      <jats:italic toggle=\"yes\">MEN1<\/jats:italic>\n                      mutations were found in 7 patients (17.9%) and\n                      <jats:italic toggle=\"yes\">CDC73<\/jats:italic>\n                      mutations in 4 (10.2%).\n                      <jats:italic toggle=\"yes\">MENI<\/jats:italic>\n                      mutations included c. 1351-2A&gt;G, c. 249_252del (p.Ile85fs), c. 1763C&gt;T(p.S588L) and c. 415C&gt;T(p.H139Y). Clinical features in MEN1-positive patients included microprolactinomas (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 2), multiglandular disease (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 5), recurrent PHPT (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 1), persistent PHPT (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 1), and gastric neuroendocrine tumour (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 1). Among\n                      <jats:italic toggle=\"yes\">CDC73<\/jats:italic>\n                      mutation patients, 2 (50%) had familial PHPT, 2 (50%) had hyperparathyroidism jaw tumour syndrome (one had multiple bilateral renal cysts and one had multiple uterine leiomyomas); however, none had either ossifying fibroma of the jaw. Identified\n                      <jats:italic toggle=\"yes\">CDC73<\/jats:italic>\n                      mutations included c. 664C&gt;T(p.R222X), c. 415C&gt;T(p.R139X), c. 687_688dellAG(p.Arg229Serfs37), and c76delA(p.Ile26SerfsX11). The mutations were statistically associated with age, higher serum calcium levels, elevated ALP, and greater skeletal involvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>For optimal management, PHPT patients with high-risk features should be subjected to customised genetic testing in resource-limited settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijem.ijem_620_25","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:00:10Z","timestamp":1766152810000},"page":"659-666","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Next-Generation Sequencing of MEN 1, RET, CDC 73, and CDKNIB Genes in Familial Primary Hyperparathyroidism: A Study from Northern India"],"prefix":"10.4103","volume":"29","author":[{"given":"Ajaz","family":"Qadir","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raiz A.","family":"Misgar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Chhabra","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imtiyaz A.","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mir I.","family":"Bashir","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshad I.","family":"Wani","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munir A.","family":"Wani","sequence":"additional","affiliation":[{"name":"Department of General and Minimal Invasive Surgery, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajaz A.","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of General and Minimal Invasive Surgery, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javid A.","family":"Sofi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"R1-20251220","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.1210\/jc.2018-01225","article-title":"Primary hyperparathyroidism","volume":"103","author":"Bilezikian","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"R2-20251220","doi-asserted-by":"crossref","first-page":"623667","DOI":"10.3389\/fendo.2021.623667","article-title":"Familial hyperparathyroidism","volume":"12","author":"Blau","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"R3-20251220","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1210\/jc.2014-1413","article-title":"Guidelines for the management of asymptomatic primary hyperparathyroidism:Summary statement from the Fourth International Workshop","volume":"99","author":"Bilezikian","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"R4-20251220","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1056\/NEJM198907273210403","article-title":"Association of parathyroid tumors in multiple endocrine neoplasia type 1 with loss of alleles on chromosome 11","volume":"321","author":"Thakker","year":"1989","journal-title":"N Engl J Med"},{"key":"R5-20251220","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s12020-021-02927-3","article-title":"A contemporary clinical approach to genetic testing for heritable hyperparathyroidism syndromes","volume":"75","author":"De Sousa","year":"2022","journal-title":"Endocrine"},{"key":"R6-20251220","doi-asserted-by":"crossref","first-page":"60","DOI":"10.11138\/ccmbm\/2017.14.1.060","article-title":"Molecular genetics in primary hyperparathyroidism:The role of genetic tests in differential diagnosis, disease prevention strategy, and therapeutic planning","volume":"14","author":"Marini","year":"2017","journal-title":"A 2017 update. Clin Cases Miner Bone Metab"},{"key":"R7-20251220","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1210\/jc.2003-030675","article-title":"Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome","volume":"89","author":"Simonds","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"R8-20251220","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1001\/jamasurg.2016.2310","article-title":"The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism","volume":"151","author":"Wilhelm","year":"2016","journal-title":"JAMA Surg"},{"key":"R9-20251220","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00423-015-1342-7","article-title":"Hereditary hyperparathyroidism--A consensus report of the European Society of Endocrine Surgeons (ESES)","volume":"400","author":"Iacobone","year":"2015","journal-title":"Langenbecks Arch Surg"},{"key":"R10-20251220","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1002\/jbmr.4665","article-title":"Epidemiology, pathophysiology and genetics of primary hyperparathyroidism","volume":"37","author":"Minisola","year":"2022","journal-title":"J Bone Miner Res"},{"key":"R11-20251220","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/BF01622200","article-title":"Assessment of fracture risk and its application to screening for postmenopausal osteoporosis:Synopsis of a WHO report","volume":"4","author":"Kanis","year":"1994","journal-title":"WHO Study Group. Osteoporos Int"},{"key":"R12-20251220","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants:A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"R13-20251220","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4103\/jhrs.JHRS_42_19","article-title":"Multiple uterine leiomyomas in multiple endocrine neoplasia type 1 with a novel MEN1 gene mutation","volume":"13","author":"Misgar","year":"2020","journal-title":"J Hum Reprod Sci"},{"key":"R14-20251220","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 gene next-generation sequencing","volume":"179","author":"Carvalho","year":"2018","journal-title":"Eur J Endocrinol"},{"key":"R15-20251220","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1056\/NEJMoa031237","article-title":"Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma","volume":"349","author":"Shattuck","year":"2003","journal-title":"N Engl J Med"},{"key":"R16-20251220","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1530\/EJE-06-0720","article-title":"Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma?","volume":"156","author":"Cetani","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"R17-20251220","doi-asserted-by":"crossref","first-page":"4534","DOI":"10.1210\/jc.2017-01249","article-title":"CDC73-related disorders:Clinical manifestations and case detection in primary hyperparathyroidism","volume":"102","author":"Van der Tuin","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"R18-20251220","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1136\/jmg.40.9.657","article-title":"HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours","volume":"40","author":"Howell","year":"2003","journal-title":"JMed Genet"},{"key":"R19-20251220","doi-asserted-by":"crossref","first-page":"1244361","DOI":"10.3389\/fendo.2023.1244361","article-title":"Genetic testing for familial hyperparathyroidism:Clinical-genetic profile in a Mediterranean cohort","volume":"14","author":"Mazarico-Altisent","year":"2023","journal-title":"Front Endocrinol"},{"key":"R20-20251220","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s12672-011-0100-8","article-title":"Frequent germ-line mutations of the MEN1, CASR, and HRPT2\/CDC73 genes in young patients with clinically non-familial primary hyperparathyroidism","volume":"3","author":"Starker","year":"2012","journal-title":"Horm Cancer"},{"key":"R21-20251220","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/cen.14254","article-title":"Genetic testing for hereditary hyperparathyroidism and familial hypocalciuric hypercalcaemia in a large UK cohort","volume":"93","author":"Mariathasan","year":"2020","journal-title":"Clin Endocrinol (Oxf)"},{"key":"R22-20251220","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.jamcollsurg.2018.01.007","article-title":"Probability of positive genetic testing results in patients with family history of primary hyperparathyroidism","volume":"226","author":"El Lakis","year":"2018","journal-title":"J Am Coll Surg"},{"key":"R23-20251220","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/ng0897-375","article-title":"Somatic mutation of the MEN1 gene in parathyroid tumours","volume":"16","author":"Heppner","year":"1997","journal-title":"Nat Genet"},{"key":"R24-20251220","first-page":"2627","article-title":"Alterations of the MEN1 gene in sporadic parathyroid tumors","volume":"83","author":"Farnebo","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"R25-20251220","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1007\/BF03346498","article-title":"Mutation analysis of MEN1, HRPT2, CASR, CDKN1B, and AIP genes in primary hyperparathyroidism patients with features of genetic predisposition","volume":"32","author":"Vierimaa","year":"2009","journal-title":"J Endocrinol Invest"},{"key":"R26-20251220","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1002\/jbmr.4653","article-title":"Multilevel annotation of germline MEN1 variants of synonymous, nonsynonymous, and uncertain significance in indian patients with sporadic primary hyperparathyroidism","volume":"37","author":"Kaur","year":"2022","journal-title":"J Bone Miner Res"},{"key":"R27-20251220","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.4158\/EP15648.OR","article-title":"HRPT2- (CDC73) related hereditary hyperparathyroidism:A case series from Western India","volume":"21","author":"Khadilkar","year":"2015","journal-title":"Endocr Pract"},{"key":"R28-20251220","doi-asserted-by":"crossref","first-page":"R441","DOI":"10.1530\/ERC-19-0135","article-title":"Atypical parathyroid adenomas:Challenging lesions in the differential diagnosis of endocrine tumors","volume":"26","author":"Cetani","year":"2019","journal-title":"Endocr Relat Cancer"},{"issue":"Suppl 1","key":"R29-20251220","doi-asserted-by":"crossref","first-page":"86s","DOI":"10.1016\/S0753-3322(00)80020-7","article-title":"Clinical aspects of hyperparathyroidism in Japanese multiple endocrine neoplasia type 1","volume":"54","author":"Sato","year":"2000","journal-title":"Biomed Pharmacother"},{"key":"R30-20251220","first-page":"1119","article-title":"Osteoporosis in multiple endocrine neoplasia type 1:Severity, clinical significance, relationship to primary hyperparathyroidism, and response to parathyroidectomy","volume":"134","author":"Burgess","year":"1999","journal-title":"Arch Surg Chic Ill 1960"},{"key":"R31-20251220","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1359\/jbmr.090304","article-title":"Sporadic and MEN1-related primary hyperparathyroidism:Differences in clinical expression and severity","volume":"24","author":"Eller-Vainicher","year":"2009","journal-title":"J Bone Miner Res"},{"key":"R32-20251220","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 western India","volume":"15","author":"Goroshi","year":"2016","journal-title":"Fam Cancer"},{"key":"R33-20251220","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s00223-022-00985-x","article-title":"Genotype-phenotype correlations in Asian Indian children and adolescents with primary hyperparathyroidism","volume":"111","author":"Sharma","year":"2022","journal-title":"Calcif Tissue Int"},{"key":"R34-20251220","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/jbmr.4883","article-title":"Genetic and clinical screening for hereditary primary hyperparathyroidism in a large Chinese cohort:A single-center study","volume":"38","author":"Song","year":"2023","journal-title":"J Bone Miner Res"}],"container-title":["Indian Journal of Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijem.ijem_620_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:52:20Z","timestamp":1786647140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijem.ijem_620_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/ijem.ijem_620_25","relation":{},"ISSN":["2230-8210","2230-9500"],"issn-type":[{"value":"2230-8210","type":"print"},{"value":"2230-9500","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-07-04","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-03","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}