Genetics of hereditary forms of primary hyperparathyroidism.

Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101142469 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2520-8721 (Electronic) Linking ISSN: 11093099 NLM ISO Abbreviation: Hormones (Athens) Subsets: MEDLINE

Publication: <2018-> : [Cham] : Springer International Publishing
Original Publication: Athens, Greece : Hellenic Endocrine Society, [2002]-

Hyperparathyroidism, Primary*/diagnosis ; Hypercalcemia* ; Adenoma* ; Fibroma* ; Hyperparathyroidism* ; Jaw Neoplasms*; Infant, Newborn ; Humans ; Calcium

Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH) concentrations, may occur as part of a hereditary syndromic disorder or as a non-syndromic disease. The associated syndromic disorders include multiple endocrine neoplasia types 1-5 (MEN1-5) and hyperparathyroidism with jaw tumor (HPT-JT) syndromes, and the non-syndromic forms include familial hypocalciuric hypercalcemia types 1-3 (FHH1-3), familial isolated hyperparathyroidism (FIHP), and neonatal severe hyperparathyroidism (NS-HPT). Such hereditary forms may occur in > 10% of patients with PHPT, and their recognition is important for implementation of gene-specific screening protocols and investigations for other associated tumors. Syndromic PHPT tends to be multifocal and multiglandular with most patients requiring parathyroidectomy with the aim of limiting end-organ damage associated with hypercalcemia, particularly osteoporosis, nephrolithiasis, and renal failure. Some patients with non-syndromic PHPT may have mutations of the MEN1 gene or the calcium-sensing receptor (CASR), whose loss of function mutations usually cause FHH1, a disorder associated with mild hypercalcemia and may follow a benign clinical course. Measurement of the urinary calcium-to-creatinine ratio clearance (UCCR) may help to distinguish patients with FHH from those with PHPT, as the majority of FHH patients have low urinary calcium excretion (UCCR < 0.01). Once genetic testing confirms a hereditary cause of PHPT, further genetic testing can be offered to the patients' relatives and subsequent screening can be carried out in these affected family members, which prevents inappropriate testing in normal individuals.
(© 2023. The Author(s).)

Soto-Pedre E, Newey PJ, Leese GP (2023) Stable incidence and increasing prevalence of primary hyperparathyroidism in a population-based study in Scotland. J Clin Endocrinol Metab 108(10):e1117–e1124. https://doi.org/10.1210/clinem/dgad201. (PMID: 10.1210/clinem/dgad2013702297510505547)
Press DM, Siperstein AE, Berber E, Shin JJ, Metzger R, Monteiro R, Mino J, Swagel W, Mitchell JC (2013) The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record. Surgery 154(6):1232–7. https://doi.org/10.1016/j.surg.2013.06.051 . (discussion 7-8). (PMID: 10.1016/j.surg.2013.06.05124383100)
Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML, Endocrine S (2012) Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 97(9):2990–3011. https://doi.org/10.1210/jc.2012-1230. (PMID: 10.1210/jc.2012-123022723327)
Eastell R, Brandi ML, Costa AG, D’Amour P, Shoback DM, Thakker RV (2014) Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab 99(10):3570–3579. https://doi.org/10.1210/jc.2014-1414. (PMID: 10.1210/jc.2014-141425162666)
Bilezikian JP (2018) Primary Hyperparathyroidism. J Clin Endocrinol Metab 103(11):3993–4004. https://doi.org/10.1210/jc.2018-01225. (PMID: 10.1210/jc.2018-01225300602266182311)
Thakker RV (2016) Genetics of parathyroid tumours. J Intern Med 280(6):574–583. https://doi.org/10.1111/joim.12523. (PMID: 10.1111/joim.1252327306766)
Wermers RA, Khosla S, Atkinson EJ, Achenbach SJ, Oberg AL, Grant CS, Melton LJ 3rd (2006) Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993–2001: an update on the changing epidemiology of the disease. J Bone Miner Res 21(1):171–177. https://doi.org/10.1359/jbmr.050910. (PMID: 10.1359/jbmr.05091016355286)
Yeh MW, Ituarte PH, Zhou HC, Nishimoto S, Liu IL, Harari A, Haigh PI, Adams AL (2013) Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab 98(3):1122–1129. https://doi.org/10.1210/jc.2012-4022. (PMID: 10.1210/jc.2012-4022234183153590475)
Walker MD, Silverberg SJ (2018) Primary hyperparathyroidism. Nat Rev Endocrinol 14(2):115–125. https://doi.org/10.1038/nrendo.2017.104. (PMID: 10.1038/nrendo.2017.10428885621)
Lemos MC, Thakker RV (2008) Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat 29(1):22–32. https://doi.org/10.1002/humu.20605. (PMID: 10.1002/humu.2060517879353)
Hannan FM, Nesbit MA, Christie PT, Fratter C, Dudley NE, Sadler GP, Thakker RV (2008) Familial isolated primary hyperparathyroidism caused by mutations of the MEN1 gene. Nat Clin Pract Endocrinol Metab 4(1):53–58. https://doi.org/10.1038/ncpendmet0718. (PMID: 10.1038/ncpendmet071818084346)
Hannan FM, Nesbit MA, Christie PT, Lissens W, Van der Schueren B, Bex M, Bouillon R, Thakker RV (2010) A homozygous inactivating calcium-sensing receptor mutation, Pro339Thr, is associated with isolated primary hyperparathyroidism: correlation between location of mutations and severity of hypercalcaemia. Clin Endocrinol (Oxf) 73(6):715–722. https://doi.org/10.1111/j.1365-2265.2010.03870.x. (PMID: 10.1111/j.1365-2265.2010.03870.x20846291)
Halperin R, Arnon L, Nasirov S, Friedensohn L, Gershinsky M, Telerman A, Friedman E, Bernstein-Molho R, Tirosh A (2023) Germline CDKN1B variant type and site are associated with phenotype in MEN4. Endocr Relat Cancer 30(1):e220174. https://doi.org/10.1530/erc-22-0174. (PMID: 10.1530/erc-22-017436256846)
Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Albert L, Cano A, Pareja R, Caixàs A, Rigla M (2023) Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism. J Endocrinol Invest 46(4):829–840. https://doi.org/10.1007/s40618-022-01948-7. (PMID: 10.1007/s40618-022-01948-736334246)
Burnichon N, Cascon A, Schiavi F, Morales NP, Comino-Mendez I, Abermil N et al (2012) MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res 18(10):2828–2837. https://doi.org/10.1158/1078-0432.CCR-12-0160. (PMID: 10.1158/1078-0432.CCR-12-016022452945)
Seabrook AJ, Harris JE, Velosa SB, Kim E, McInerney-Leo AM, Dwight T et al (2021) Multiple endocrine tumors associated with germline MAX mutations: multiple endocrine neoplasia type 5? J Clin Endocrinol Metab 106(4):1163–1182. https://doi.org/10.1210/clinem/dgaa957. (PMID: 10.1210/clinem/dgaa95733367756)
Roszko KL, Blouch E, Blake M, Powers JF, Tischler AS, Hodin R et al (2017) Case report of a prolactinoma in a patient with a novel MAX mutation and bilateral pheochromocytomas. J Endocr Soc 1(11):1401–1407. https://doi.org/10.1210/js.2017-00135. (PMID: 10.1210/js.2017-00135292644635686672)
Petignot S, Daly AF, Castermans E, Korpershoek E, Scagnol I, Beckers P et al (2020) Pancreatic neuroendocrine neoplasm associated with a familial MAX deletion. Horm Metab Res 52(11):784–787. https://doi.org/10.1055/a-1186-0790. (PMID: 10.1055/a-1186-079032521546)
Daly AF, Castermans E, Oudijk L, Guitelman MA, Beckers P, Potorac I et al (2018) Pheochromocytomas and pituitary adenomas in three patients with MAX exon deletions. Endocr Relat Cancer 25(5):L37-l42. https://doi.org/10.1530/erc-18-0065. (PMID: 10.1530/erc-18-006529535143)
Charoenngam N, Mannstadt M (2023) Primary hyperparathyroidism in a patient with bilateral pheochromocytoma and a mutation in the tumor suppressor MAX. JCEM Case Rep 1(1). https://doi.org/10.1210/jcemcr/luad006.
Kobza AO, Dizon S, Arnaout A (2018) Case report of bilateral pheochromocytomas due to a novel max mutation in a patient known to have a pituitary prolactinoma. AACE Clinical Case Rep 4(6):e453–e456. https://doi.org/10.4158/ACCR-2018-0146. (PMID: 10.4158/ACCR-2018-0146)
Mamedova E, Vasilyev E, Petrov V, Buryakina S, Tiulpakov A, Belaya Z (2021) Familial acromegaly and bilateral asynchronous pheochromocytomas in a female patient with a MAX mutation: a case report. Front Endocrinol (Lausanne) 12:683492. https://doi.org/10.3389/fendo.2021.683492. (PMID: 10.3389/fendo.2021.68349234135865)
Tora R, Welch J, Sun J, Agarwal SK, Bell DA, Merino M, Weinstein LS, Simonds WF, Jha S (2023) Phenotypic profiling and molecular mechanisms in hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab dgad368. https://doi.org/10.1210/clinem/dgad368.
van der Tuin K, Tops CMJ, Adank MA, Cobben J-M, Hamdy NAT, Jongmans MC et al (2017) CDC73-related disorders: clinical manifestations and case detection in primary hyperparathyroidism. J Clin Endocrinol Metab 102(12):4534–4540. https://doi.org/10.1210/jc.2017-01249. (PMID: 10.1210/jc.2017-0124929040582)
Erickson LA, Mete O, Juhlin CC, Perren A, Gill AJ (2022) Overview of the 2022 WHO classification of parathyroid tumors. Endocrine Pathol 33(1):64–89. https://doi.org/10.1007/s12022-022-09709-1. (PMID: 10.1007/s12022-022-09709-1)
Shattuck TM, Valimaki S, Obara T, Gaz RD, Clark OH, Shoback D, Wierman ME, Tojo K, Robbins CM, Carpten JD, Farnebo LO, Larsson C, Arnold A (2003) Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 349(18):1722–1729. https://doi.org/10.1056/NEJMoa031237. (PMID: 10.1056/NEJMoa03123714585940)
Hannan FM, Nesbit MA, Zhang C, Cranston T, Curley AJ, Harding B, Fratter C, Rust N, Christie PT, Turner JJ, Lemos MC, Bowl MR, Bouillon R, Brain C, Bridges N, Burren C, Connell JM, Jung H, Marks E, McCredie D, Mughal Z, Rodda C, Tollefsen S, Brown EM, Yang JJ, Thakker RV (2012) Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum Mol Genet 21(12):2768–2778. https://doi.org/10.1093/hmg/dds105. (PMID: 10.1093/hmg/dds10522422767)
Newey PJ, Bowl MR, Cranston T, Thakker RV (2010) Cell division cycle protein 73 homolog (CDC73) mutations in the hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid tumors. Hum Mutat 31(3):295–307. https://doi.org/10.1002/humu.21188. (PMID: 10.1002/humu.2118820052758)
Bricaire L, Odou MF, Cardot-Bauters C, Delemer B, North MO, Salenave S, Vezzosi D, Kuhn JM, Murat A, Caron P, Sadoul JL, Silve C, Chanson P, Barlier A, Clauser E, Porchet N, Groussin L, GroupGTE (2013) Frequent large germline HRPT2 deletions in a French national cohort of patients with primary hyperparathyroidism. J Clin Endocrinol Metab 98(2):E403-8. https://doi.org/10.1210/jc.2012-2789. (PMID: 10.1210/jc.2012-278923293331)
Khosla S, Ebeling PR, Firek AF, Burritt MM, Kao PC, Heath H 3rd (1993) Calcium infusion suggests a “set-point” abnormality of parathyroid gland function in familial benign hypercalcemia and more complex disturbances in primary hyperparathyroidism. J Clin Endocrinol Metab 76(3):715–720. https://doi.org/10.1210/jcem.76.3.8445032. (PMID: 10.1210/jcem.76.3.84450328445032)
Singh P, Bhadada SK, Dahiya D, Arya AK, Saikia UN, Sachdeva N, Kaur J, Brandi ML, Rao SD (2020) Reduced calcium sensing receptor (CaSR) expression is epigenetically deregulated in parathyroid adenomas. J Clin Endocrinol Metab 105(9):3015–3024. https://doi.org/10.1210/clinem/dgaa419. (PMID: 10.1210/clinem/dgaa419326098277500582)
Eldeiry LS, Ruan DT, Brown EM, Gaglia JL, Garber JR (2012) Primary hyperparathyroidism and familial hypocalciuric hypercalcemia: relationships and clinical implications. Endocr Pract 18(3):412–417. https://doi.org/10.4158/EP11272.RA. (PMID: 10.4158/EP11272.RA22232026)
Al-Salameh A, Cadiot G, Calender A, Goudet P, Chanson P (2021) Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol 17(4):207–224. https://doi.org/10.1038/s41574-021-00468-3. (PMID: 10.1038/s41574-021-00468-333564173)
Romanet P, Mohamed A, Giraud S, Odou MF, North MO, Pertuit M, Pasmant E, Coppin L, Guien C, Calender A, Borson-Chazot F, Beroud C, Goudet P, Barlier A (2019) UMD-MEN1 database: an overview of the 370 MEN1 variants present in 1676 patients from the French population. J Clin Endocrinol Metab 104(3):753–764. https://doi.org/10.1210/jc.2018-01170. (PMID: 10.1210/jc.2018-0117030339208)
Machens A, Schaaf L, Karges W, Frank-Raue K, Bartsch DK, Rothmund M, Schneyer U, Goretzki P, Raue F, Dralle H (2007) Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers. Clin Endocrinol (Oxf) 67(4):613–622. https://doi.org/10.1111/j.1365-2265.2007.02934.x. (PMID: 10.1111/j.1365-2265.2007.02934.x17590169)
Concolino P, Costella A, Capoluongo E (2016) Multiple endocrine neoplasia type 1 (MEN1): an update of 208 new germline variants reported in the last nine years. Cancer Gene 209(1–2):36–41. https://doi.org/10.1016/j.cancergen.2015.12.002. (PMID: 10.1016/j.cancergen.2015.12.002)
Dreijerink KM, Varier RA, van Nuland R, Broekhuizen R, Valk GD, van der Wal JE, Lips CJ, Kummer JA, Timmers HT (2009) Regulation of vitamin D receptor function in MEN1- related parathyroid adenomas. Mol Cell Endocrinol 313(1–2):1–8. https://doi.org/10.1016/j.mce.2009.08.020. (PMID: 10.1016/j.mce.2009.08.02019729047)
Yuan Z, Sánchez Claros C, Suzuki M, Maggi EC, Kaner JD, Kinstlinger N, Gorecka J, Quinn TJ, Geha R, Corn A, Pastoriza J, Jing Q, Adem A, Wu H, Alemu G, Du YC, Zheng D, Greally JM, Libutti SK (2016) Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis. Oncotarget 7(11):12633–12650. https://doi.org/10.18632/oncotarget.7279. (PMID: 10.18632/oncotarget.7279268714724914310)
de Laat JM, van der Luijt RB, Pieterman CR, Oostveen MP, Hermus AR, Dekkers OM, de Herder WW, van der Horst-Schrivers AN, Drent ML, Bisschop PH, Havekes B, Vriens MR, Valk GD (2016) MEN1 redefined, a clinical comparison of mutation-positive and mutation- negative patients. BMC Med 14(1):182. https://doi.org/10.1186/s12916-016-0708-1. (PMID: 10.1186/s12916-016-0708-1278425545109674)
Agarwal SK, Mateo CM, Marx SJ (2009) Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states. J Clin Endocrinol Metab 94(5):1826–1834. https://doi.org/10.1210/jc.2008-2083. (PMID: 10.1210/jc.2008-2083191415852684477)
Kooblall KG, Boon H, Cranston T, Stevenson M, Pagnamenta AT, Rogers A, Grozinsky- Glasberg S, Richardson T, Flanagan DE, Genomics England Research C, Taylor JC, Lines KE, Thakker RV (2021) Multiple endocrine neoplasia type 1 (MEN1) 5′UTR deletion, in MEN1 family, decreases menin expression. J Bone Miner Res 36(1):100–9. https://doi.org/10.1002/jbmr.4156. (PMID: 10.1002/jbmr.415632780883)
de Laat JM, van Leeuwaarde RS, Valk GD (2018) The importance of an early and accurate MEN1 diagnosis. Front Endocrinol (Lausanne) 9:533. https://doi.org/10.3389/fendo.2018.00533. (PMID: 10.3389/fendo.2018.0053330254610)
Mathiesen JS, Effraimidis G, Rossing M, Rasmussen ÅK, Hoejberg L, Bastholt L, Godballe C, Oturai P, Feldt-Rasmussen U (2022) Multiple endocrine neoplasia type 2: a review. Semin Cancer Biol 79:163–179. https://doi.org/10.1016/j.semcancer.2021.03.035. (PMID: 10.1016/j.semcancer.2021.03.03533812987)
Raue F, Frank-Raue K (2012) Genotype-phenotype correlation in multiple endocrine neoplasia type 2. Clinics (Sao Paulo) 67(Suppl 1):69–75. https://doi.org/10.6061/clinics/2012(sup01)13. (PMID: 10.6061/clinics/2012(sup01)1322584709)
Mulligan LM, Eng C, Healey CS, Clayton D, Kwok JBJ, Gardner E, Ponder MA, Frilling A, Jackson CE, Lehnert H, Neumann HPH, Thibodeau SN, Ponder BAJ (1994) Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC. Nature Genet 6(1):70–74. https://doi.org/10.1038/ng0194-70. (PMID: 10.1038/ng0194-707907913)
Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjöld M, Komminoth P, Hendy GN, Mulligan LM et al (1996) The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis JAMA 276(19):1575–1579. (PMID: 8918855)
Thakker RV (2014) Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol Cell Endocrinol 386(1–2):2–15. https://doi.org/10.1016/j.mce.2013.08.002. (PMID: 10.1016/j.mce.2013.08.002239331184082531)
Singeisen H, Renzulli MM, Pavlicek V, Probst P, Hauswirth F, Muller MK, Adamczyk M, Weber A, Kaderli RM, Renzulli P (2023) Multiple endocrine neoplasia type 4: a new member of the MEN family. Endocr Connect 12(2):e220411. https://doi.org/10.1530/ec-22-0411. (PMID: 10.1530/ec-22-0411365206839874964)
Fritz A, Walch A, Piotrowska K, Rosemann M, Schäffer E, Weber K, Timper A, Wildner G, Graw J, Höfler H (2002) Recessive transmission of a multiple endocrine neoplasia syndrome in the rat. Cancer Res 62(11):3048–3051. (PMID: 12036912)
Pellegata N, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Höfler H, Fend F, Graw J, Atkinson M (2006) Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci USA 103(42):15558-15563. https://doi.org/10.1073/pnas.0603877103.
Carroll PA, Freie BW, Mathsyaraja H, Eisenman RN (2018) The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis. Front Med 12(4):412–425. https://doi.org/10.1007/s11684-018-0650-z. (PMID: 10.1007/s11684-018-0650-z300548537358075)
Comino-Méndez I, Gracia-Aznárez FJ, Schiavi F, Landa I, Leandro-García LJ, Letón R et al (2011) Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet 43(7):663–667. https://doi.org/10.1038/ng.861. (PMID: 10.1038/ng.86121685915)
Minisola S, Arnold A, Belaya Z, Brandi ML, Clarke BL, Hannan FM, Hofbauer LC, Insogna KL, Lacroix A, Liberman U, Palermo A, Pepe J, Rizzoli R, Wermers R, Thakker RV (2022) Epidemiology, pathophysiology, and genetics of primary hyperparathyroidism. J Bone Miner Res 37(11):2315–2329. https://doi.org/10.1002/jbmr.4665. (PMID: 10.1002/jbmr.466536245271)
Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J et al (2002) HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome. Nat Genet 32(4):676–680. https://doi.org/10.1038/ng1048. (PMID: 10.1038/ng104812434154)
Cavaco BM, Barros L, Pannett AA, Ruas L, Carvalheiro M, Ruas MM, Krausz T, Santos MA, Sobrinho LG, Leite V, Thakker RV (2001) The hyperparathyroidism-jaw tumour syndrome in a Portuguese kindred. QJM 94(4):213–222. https://doi.org/10.1093/qjmed/94.4.213. (PMID: 10.1093/qjmed/94.4.21311294964)
Jackson CE, Norum RA, Boyd SB, Talpos GB, Wilson SD, Taggart RT, Mallette LE (1990) Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome. Surgery 108(6):1006–12 (discussion 12-3). (PMID: 2123361)
Rozenblatt-Rosen O, Hughes CM, Nannepaga SJ, Shanmugam KS, Copeland TD, Guszczynski T, Resau JH, Meyerson M (2005) The parafibromin tumor suppressor protein is part of a human Paf1 complex. Mol Cell Biol 25(2):612–620. https://doi.org/10.1128/MCB.25.2.612-620.2005. (PMID: 10.1128/MCB.25.2.612-620.200515632063543415)
Yart A, Gstaiger M, Wirbelauer C, Pecnik M, Anastasiou D, Hess D, Krek W (2005) The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Mol Cell Biol 25(12):5052–5060. https://doi.org/10.1128/MCB.25.12.5052-5060.2005. (PMID: 10.1128/MCB.25.12.5052-5060.2005159236221140601)
Woodard GE, Lin L, Zhang J-H, Agarwal SK, Marx SJ, Simonds WF (2005) Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene 24(7):1272–1276. https://doi.org/10.1038/sj.onc.1208274. (PMID: 10.1038/sj.onc.120827415580289)
Yang Y-J, Han J-W, Youn H-D, Cho E (2009) The tumor suppressor, parafibromin, mediates histone H3 K9 methylation for cyclin D1 repression. Nucleic Acids Res 38(2):382–390. https://doi.org/10.1093/nar/gkp991. (PMID: 10.1093/nar/gkp991199067182811029)
Lin L, Zhang J-H, Panicker LM, Simonds WF (2008) The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto- oncogene. Proc Natl Acad Sci USA 105(45):17420-5 https://doi.org/10.1073/pnas.0710725105.
Bradley KJ, Cavaco BM, Bowl MR, Harding B, Cranston T, Fratter C, Besser GM, Conceicao Pereira M, Davie MW, Dudley N, Leite V, Sadler GP, Seller A, Thakker RV (2006) Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours. Clin Endocrinol (Oxf) 64(3):299–306. https://doi.org/10.1111/j.1365-2265.2006.02460.x. (PMID: 10.1111/j.1365-2265.2006.02460.x16487440)
Weaver TD, Shakir MKM, Hoang TD (2021) Hyperparathyroidism-Jaw Tumor Syndrome. Case Rep Oncol 14(1):29–33. https://doi.org/10.1159/000510002. (PMID: 10.1159/000510002337907627989853)
Frank-Raue K, Leidig-Bruckner G, Haag C, Schulze E, Lorenz A, Schmitz-Winnenthal H, Raue F (2011) Inactivating calcium-sensing receptor mutations in patients with primary hyperparathyroidism. Clin Endocrinol (Oxf) 75(1):50–5. https://doi.org/10.1111/j.1365-2265.2011.04059.x. (PMID: 10.1111/j.1365-2265.2011.04059.x21521328)
Guan B, Welch JM, Sapp JC, Ling H, Li Y, Johnston JJ, Kebebew E, Biesecker LG, Simonds WF, Marx SJ, Agarwal SK (2016) GCM2-activating mutations in familial isolated hyperparathyroidism. Am J Hum Genet 99(5):1034–1044. https://doi.org/10.1016/j.ajhg.2016.08.018. (PMID: 10.1016/j.ajhg.2016.08.018277458355097944)
Guan B, Welch JM, Vemulapalli M, Li Y, Ling H, Kebebew E, Simonds WF, Marx SJ, Agarwal SK (2017) Ethnicity of patients with germline GCM2-activating variants and primary hyperparathyroidism. J Endocr Soc 1(5):488–499. https://doi.org/10.1210/js.2017-00043. (PMID: 10.1210/js.2017-00043292645045686704)
Gunther T, Chen ZF, Kim J, Priemel M, Rueger JM, Amling M, Moseley JM, Martin TJ, Anderson DJ, Karsenty G (2000) Genetic ablation of parathyroid glands reveals another source of parathyroid hormone. Nature 406(6792):199–203. https://doi.org/10.1038/35018111. (PMID: 10.1038/3501811110910362)
García-Castaño A, Madariaga L, Gómez-Conde S, Cordo CLR, López-Iglesias M, Garcia-Fernández Y et al (2021) Five patients with disorders of calcium metabolism presented with GCM2 gene variants. Sci Rep 11(1):2968. https://doi.org/10.1038/s41598-021-82661-y. (PMID: 10.1038/s41598-021-82661-y335365787859196)
Riccardi A, Aspir T, Shen L, Kuo CL, Brown TC, Korah R, Murtha TD, Bellizzi J, Parham K, Carling T, Costa-Guda J, Arnold A (2019) Analysis of activating GCM2 sequence variants in sporadic parathyroid adenomas. J Clin Endocrinol Metab 104(6):1948–1952. https://doi.org/10.1210/jc.2018-02517. (PMID: 10.1210/jc.2018-0251730624640)
Vincze S, Peters NV, Kuo CL, Brown TC, Korah R, Murtha TD, Bellizzi J, Riccardi A, Parham K, Carling T, Costa-Guda J, Arnold A (2022) GCM2 variants in familial and multiglandular primary hyperparathyroidism. J Clin Endocrinol Metab 107(5):e2021–e2026. https://doi.org/10.1210/clinem/dgab929. (PMID: 10.1210/clinem/dgab92934967908)
Dershem R, Gorvin CM, Metpally RPR, Krishnamurthy S, Smelser DT, Hannan FM, Carey DJ, Thakker RV, Breitwieser GE, Regeneron Genetics C (2020) Familial hypocalciuric hypercalcemia type 1 and autosomal-dominant hypocalcemia type 1: prevalence in a large healthcare population. Am J Hum Genet 106(6):734–747. https://doi.org/10.1016/j.ajhg.2020.04.006. (PMID: 10.1016/j.ajhg.2020.04.006323865597273533)
Nesbit MA, Hannan FM, Howles SA, Babinsky VN, Head RA, Cranston T, Rust N, Hobbs MR, Heath H 3rd, Thakker RV (2013) Mutations affecting G-protein subunit alpha11 in hypercalcemia and hypocalcemia. N Engl J Med 368(26):2476–2486. https://doi.org/10.1056/NEJMoa1300253. (PMID: 10.1056/NEJMoa1300253238025163773604)
Nesbit MA, Hannan FM, Howles SA, Reed AA, Cranston T, Thakker CE, Gregory L, Rimmer AJ, Rust N, Graham U, Morrison PJ, Hunter SJ, Whyte MP, McVean G, Buck D, Thakker RV (2013) Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. Nat Genet 45(1):93–97. https://doi.org/10.1038/ng.2492. (PMID: 10.1038/ng.249223222959)
Conigrave AD, Ward DT (2013) Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways. Best Pract Res Clin Endocrinol Metab 27(3):315–331. https://doi.org/10.1016/j.beem.2013.05.010. (PMID: 10.1016/j.beem.2013.05.01023856262)
Gorvin CM, Rogers A, Hastoy B, Tarasov AI, Frost M, Sposini S, Inoue A, Whyte MP, Rorsman P, Hanyaloglu AC, Breitwieser GE, Thakker RV (2018) AP2sigma mutations impair calcium-sensing receptor trafficking and signaling, and show an endosomal pathway to spatially direct G-protein selectivity. Cell Rep 22(4):1054–1066. https://doi.org/10.1016/j.celrep.2017.12.089. (PMID: 10.1016/j.celrep.2017.12.089294201715792449)
Lee JY, Shoback DM (2018) Familial hypocalciuric hypercalcemia and related disorders. Best Pract Res Clin Endocrinol Metab 32(5):609–619. https://doi.org/10.1016/j.beem.2018.05.004. (PMID: 10.1016/j.beem.2018.05.004304495446767927)
Hannan FM, Babinsky VN, Thakker RV (2016) Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis. J Mol Endocrinol 57(3):R127–R142. https://doi.org/10.1530/JME-16-0124. (PMID: 10.1530/JME-16-0124276478395064759)
Gorvin CM, Cranston T, Hannan FM, Rust N, Qureshi A, Nesbit MA, Thakker RV (2016) A G-protein subunit-α11 loss-of-function mutation, Thr54Met, causes familial hypocalciuric hypercalcemia Type 2 (FHH2). J Bone Miner Res 31(6):1200–1206. https://doi.org/10.1002/jbmr.2778. (PMID: 10.1002/jbmr.277826729423)
Gorvin CM, Hannan FM, Cranston T, Valta H, Makitie O, Schalin-Jantti C, Thakker RV (2018) Cinacalcet rectifies hypercalcemia in a patient with familial hypocalciuric hypercalcemia type 2 (FHH2) caused by a germline loss-of-function Gα11 mutation. J Bone Miner Res 33(1):32–41. https://doi.org/10.1002/jbmr.3241. (PMID: 10.1002/jbmr.324128833550)
Howles SA, Gorvin CM, Cranston T, Rogers A, Gluck AK, Boon H, Gibson K, Rahman M, Root A, Nesbit MA, Hannan FM, Thakker RV (2023) GNA11 variants identified in patients with hypercalcemia or hypocalcemia. J Bone Miner Res 38(6):907–917. https://doi.org/10.1002/jbmr.4803. (PMID: 10.1002/jbmr.480336970776)
Gorvin CM, Metpally R, Stokes VJ, Hannan FM, Krishnamurthy SB, Overton JD, Reid JG, Breitwieser GE, Thakker RV (2018) Large-scale exome datasets reveal a new class of adaptor-related protein complex 2 sigma subunit (AP2sigma) mutations, located at the interface with the AP2 alpha subunit, that impair calcium-sensing receptor signalling. Hum Mol Genet 27(5):901–911. https://doi.org/10.1093/hmg/ddy010. (PMID: 10.1093/hmg/ddy010293250225982735)
Hannan FM, Thakker RV (2013) Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte and water metabolism. Best Pract Res Clin Endocrinol Metab 27(3):359–371. https://doi.org/10.1016/j.beem.2013.04.007. (PMID: 10.1016/j.beem.2013.04.00723856265)
Marx SJ (2017) Calcimimetic use in familial hypocalciuric hypercalcemia—a perspective in endocrinology. J Clin Endocrinol Metab 102(11):3933–3936. https://doi.org/10.1210/jc.2017-01606. (PMID: 10.1210/jc.2017-01606289458575673268)
Howles SA, Hannan FM, Babinsky VN, Rogers A, Gorvin CM, Rust N, Richardson T, McKenna MJ, Nesbit MA, Thakker RV (2016) Cinacalcet for symptomatic hypercalcemia caused by AP2S1 mutations. New Engl J Med 374(14):1396–1398. https://doi.org/10.1056/NEJMc1511646. (PMID: 10.1056/NEJMc151164627050234)
Gannon AW, Monk HM, Levine MA (2014) Cinacalcet monotherapy in neonatal severe hyperparathyroidism: a case study and review. J Clin Endocrinol Metab 99(1):7–11. https://doi.org/10.1210/jc.2013-2834. (PMID: 10.1210/jc.2013-283424203066)
Reh CM, Hendy GN, Cole DE, Jeandron DD (2011) Neonatal hyperparathyroidism with a heterozygous calcium-sensing receptor (CASR) R185Q mutation: clinical benefit from cinacalcet. J Clin Endocrinol Metab 96(4):E707–E712. https://doi.org/10.1210/jc.2010-1306. (PMID: 10.1210/jc.2010-130621289269)
Fisher MM, Cabrera SM, Imel EA (2015) Successful treatment of neonatal severe hyperparathyroidism with cinacalcet in two patients. Endocrinol Diabetes Metab Case Rep 2015:150040. https://doi.org/10.1530/EDM-15-0040. (PMID: 10.1530/EDM-15-0040261612614496565)
Wilhelm-Bals A, Parvex P, Magdelaine C, Girardin E (2012) Successful use of bisphosphonate and calcimimetic in neonatal severe primary hyperparathyroidism. Pediatrics 129(3):e812–e816. https://doi.org/10.1542/peds.2011-0128. (PMID: 10.1542/peds.2011-012822331334)
Gulcan-Kersin S, Kirkgoz T, Eltan M, Rzayev T, Ata P, Bilgen H, Ozek E, Bereket A, Turan S (2020) Cinacalcet as a first-line treatment in neonatal severe hyperparathyroidism secondary to calcium sensing receptor (CaSR) mutation. Horm Res Paediatr 93(5):313–321. https://doi.org/10.1159/000510623. (PMID: 10.1159/00051062333147586)
Gupta P, Tak SA, S AV, Misgar RA, Agarwala S, Jain V, Sharma R (2022) A case of neonatal severe hyperparathyroidism: challenges in management. Indian J Pediatr 89(10):1025-7 https://doi.org/10.1007/s12098-022-04169-1.
Sadacharan D, Mahadevan S, Rao SS, Kumar AP, Swathi S, Kumar S, Kannan S (2020) Neonatal severe primary hyperparathyroidism: a series of four cases and their long-term management in India. Indian J Endocrinol Metab 24(2):196–201. https://doi.org/10.4103/ijem.IJEM_53_20. (PMID: 10.4103/ijem.IJEM_53_20326997907333741)
Özgüç Çömlek F, Demir S, Gürkan H, İnan M, Sezer A, Dilek E, Kökenli F (2022) The efficiency of cinacalcet treatment in delaying parathyroidectomy in a case with neonatal severe hyperparathyroidism caused by homozygous mutation in the CASR gene. Pediatr Endocrinol Diabetes Metab 28(2):168–174. https://doi.org/10.5114/pedm.2022.115070. (PMID: 10.5114/pedm.2022.11507035399047)
Leunbach TL, Hansen AT, Madsen M, Cipliene R, Christensen PS, Schou AJ (2021) A novel case of neonatal severe hyperparathyroidism successfully treated with a type II calcimimetic drug. Bone Rep 14:100761. https://doi.org/10.1016/j.bonr.2021.100761. (PMID: 10.1016/j.bonr.2021.100761337483537972953)
Capozza M, Chinellato I, Guarnieri V, Di Lorgi N, Accadia M, Traggiai C, Mattioli G, Di Mauro A, Laforgia N (2018) Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation. BMC Pediatr 18(1):340. https://doi.org/10.1186/s12887-018-1319-0. (PMID: 10.1186/s12887-018-1319-0303768456208175)
Haider A, Sommayya A, Chaudhary S, Qadir M, Anjum MN, Saeed A et al (2021) Lack of Cinacalcet response in Neonatal Severe Hyperparathyroidism (NSHPT) due to homozygous CASR mutation. Horm Res Paediatr 94(Suppl. 1):1–445. https://doi.org/10.1159/000518849. (PMID: 10.1159/000518849)
Bilezikian JP, Khan AA, Clarke BL, Mannstadt M, Potts JT, Brandi ML (2022) The Fifth International Workshop on the Evaluation and Management of Primary Hyperparathyroidism. J Bone Miner Res 37(11):2290–2292. https://doi.org/10.1002/jbmr.4670. (PMID: 10.1002/jbmr.467036245277)
Giusti F, Cianferotti L, Gronchi G, Cioppi F, Masi L, Faggiano A, Colao A, Ferolla P, Brandi ML (2016) Cinacalcet therapy in patients affected by primary hyperparathyroidism associated to multiple endocrine neoplasia syndrome type 1 (MEN1). Endocrine 52(3):495–506. https://doi.org/10.1007/s12020-015-0696-5. (PMID: 10.1007/s12020-015-0696-526224587)
Moyes VJ, Monson JP, Chew SL, Akker SA (2010) Clinical use of cinacalcet in MEN1 hyperparathyroidism. Int J Endocrinol 2010:906163. https://doi.org/10.1155/2010/906163. (PMID: 10.1155/2010/906163205853522877200)
Falchetti A, Cilotti A, Vaggelli L, Masi L, Amedei A, Cioppi F, Tonelli F, Brandi ML (2008) A patient with MEN1-associated hyperparathyroidism, responsive to cinacalcet. Nat Clin Pract Endocrinol Metab 4(6):351–357. https://doi.org/10.1038/ncpendmet0816. (PMID: 10.1038/ncpendmet081618414463)
Larsen LV, Mirebeau-Prunier D, Imai T, Alvarez-Escola C, Hasse-Lazar K, Censi S et al (2020) Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study. Endocr Connect 9(6):489–497. https://doi.org/10.1530/ec-20-0163. (PMID: 10.1530/ec-20-0163323751207354718)
Mariathasan S, Andrews KA, Thompson E, Challis BG, Wilcox S, Pierce H et al (2020) Genetic testing for hereditary hyperparathyroidism and familial hypocalciuric hypercalcaemia in a large UK cohort. Clin Endocrinol (Oxf) 93(4):409–418. https://doi.org/10.1111/cen.14254. (PMID: 10.1111/cen.1425432430905)

C2195/A28699 United Kingdom CRUK_ Cancer Research UK

Keywords: Calcium-sensing receptor; Multiple endocrine neoplasia; PHPT; Parathyroid

SY7Q814VUP (Calcium)

Hypocalciuric hypercalcemia, familial, type 1; Hyperparathyroidism 2

Date Created: 20231201 Date Completed: 20240208 Latest Revision: 20240318

20240318

PMC10847196

10.1007/s42000-023-00508-9

38038882