{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T07:52:42Z","timestamp":1740124362790,"version":"3.37.3"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T00:00:00Z","timestamp":1521763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors that are hereditary in up to 50% of patients. The gene encoding transmembrane\u2010protein\u2010127 (<jats:italic>TMEM127<\/jats:italic>) is one of the PCC\/PGL\u2010susceptibility genes with an autosomal dominant inheritance pattern. Here, we report 2 patients with bilateral PCC who both harbored a homozygous <jats:italic>TMEM127<\/jats:italic>\u2010mutation. In a 31\u2010year\u2010old mentally retarded patient, the homozygous c.410\u20102A &gt; G mutation was discovered during an update of DNA analysis. A 26\u2010year\u2010old mentally retarded patient was found to have a homozygous c.3G &gt; A mutation. The parents of both patients were consanguineous. We reviewed previously reported clinical features of <jats:italic>TMEM127<\/jats:italic> mutation carriers and compared our findings with case descriptions of homozygous mutations in other PGL\/PCC\u2010susceptibility genes. Homozygosity for an autosomal dominant inherited disorder is an extremely rare phenomenon and has, to our knowledge, not been reported before for the gene encoding <jats:italic>TMEM127<\/jats:italic>. In the present cases, the clinical picture does not seem to be very different from heterozygous <jats:italic>TMEM127<\/jats:italic> mutation carriers, except for a relatively large tumor size and more pronounced plasma metanephrine concentration. It is unclear whether the mental retardation is causally related to homozygosity of the <jats:italic>TMEM127<\/jats:italic> mutations. Updating genetic screening in patients in whom PCC\/PGL has been diagnosed in the past should be considered as it might provide clinically relevant information.<\/jats:p>","DOI":"10.1111\/cge.13202","type":"journal-article","created":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T05:46:49Z","timestamp":1514440009000},"page":"1049-1056","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Homozygous <i>TMEM127<\/i> mutations in 2 patients with bilateral pheochromocytomas"],"prefix":"10.1111","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3597-1803","authenticated-orcid":false,"given":"K.","family":"Eijkelenkamp","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.J.W.","family":"Olderode\u2010Berends","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.B.","family":"van der Luijt","sequence":"additional","affiliation":[{"name":"Laboratory for Clinical Molecular Genetics University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Robledo","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"van Dooren","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus University Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.A.","family":"Feelders","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases Erasmus University Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.N.","family":"Kerstens","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.P.","family":"Links","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.N.A.","family":"van der Horst\u2010Schrivers","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,23]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2016.01.022"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.185"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.533"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2473"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.1830"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0114"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0758"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/imj.12088"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2012.04421.x"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3360"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.3747\/co.21.1579"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt638"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-4375"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103218"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-015-1755-2"},{"key":"e_1_2_4_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-016-0050-0"},{"key":"e_1_2_4_18_1","article-title":"Novel germline variant of TMEM127 gene in a patient with familial pheochromocytoma","volume":"2017","author":"Saitoh K","year":"2017","journal-title":"Endocrinol Diabetes Metab Case Rep."},{"key":"e_1_2_4_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0223"},{"key":"e_1_2_4_20_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-17-0359"},{"issue":"1","key":"e_1_2_4_21_1","doi-asserted-by":"crossref","first-page":"R9","DOI":"10.1530\/EJE-15-0549","article-title":"Management of endocrine disease: outcome of adrenal sparing surgery in heritable pheochromocytoma","volume":"174","author":"Castinetti F","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"e_1_2_4_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000455864"},{"key":"e_1_2_4_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101146"},{"key":"e_1_2_4_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1013"},{"key":"e_1_2_4_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101932"},{"key":"e_1_2_4_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/377108"},{"key":"e_1_2_4_27_1","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2002.123006"},{"key":"e_1_2_4_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2016.08.006"},{"key":"e_1_2_4_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.41"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13202","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T15:12:17Z","timestamp":1695568337000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,23]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1111\/cge.13202"],"URL":"https:\/\/doi.org\/10.1111\/cge.13202","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"type":"print","value":"0009-9163"},{"type":"electronic","value":"1399-0004"}],"subject":[],"published":{"date-parts":[[2018,3,23]]},"assertion":[{"value":"2017-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}