{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:28:11Z","timestamp":1789154891588,"version":"build-2803163510"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum W\u00fcrzburg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Endocrinol Invest"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The most frequent genetic alteration of familial isolated growth hormone producing pituitary neuroendocrine tumors is a germline mutation of the aryl hydrocarbon receptor-interacting protein (AIP<jats:italic>)<\/jats:italic> gene. Various <jats:italic>AIP<\/jats:italic> mutations are already known; however, an <jats:italic>AIP<\/jats:italic> mutation in exon 6 (c.811_812del; p.Arg271Glyfs*16) has not been reported yet. Here, we report a German family with two identical twins who were both affected by acromegaly and carried the above-mentioned novel <jats:italic>AIP<\/jats:italic> mutation. The father was found to be an unaffected carrier, while the paternal aunt\u00a0most likely\u00a0suffered from acromegaly as well\u00a0and died from metastatic colorectal cancer. Apart from reporting a novel <jats:italic>AIP<\/jats:italic> mutation, this study does not only highlight the different clinical and histological features of the <jats:italic>AIP<\/jats:italic> mutated growth hormone producing pituitary neuroendocrine tumors but also confirms the poor responsiveness of dopamine agonists in <jats:italic>AIP<\/jats:italic> mutated acromegaly. Furthermore, it highlights the increased mortality risk of comorbidities typically associated with acromegaly.<\/jats:p>","DOI":"10.1007\/s40618-023-02031-5","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T19:19:58Z","timestamp":1675970398000},"page":"1705-1709","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel AIP mutation in exon 6 causing acromegaly in a German family"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1490-5575","authenticated-orcid":false,"given":"M.","family":"Detomas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Altieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Flitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Saeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Korbonits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Deutschbein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"issue":"7","key":"2031_CR1","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.3390\/jcm10071377","volume":"10","author":"A Boguslawska","year":"2021","unstructured":"Boguslawska A, Korbonits M (2021) Genetics of acromegaly and gigantism. J Clin Med 10(7):1377","journal-title":"J Clin Med"},{"issue":"1","key":"2031_CR2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s11102-017-0789-7","volume":"20","author":"MR Gadelha","year":"2017","unstructured":"Gadelha MR, Kasuki L, Korbonits M (2017) The genetic background of acromegaly. Pituitary 20(1):10\u201321","journal-title":"Pituitary"},{"issue":"3","key":"2031_CR3","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1530\/ERC-11-0059","volume":"18","author":"C Villa","year":"2011","unstructured":"Villa C, Lagonigro MS, Magri F, Koziak M, Jaffrain-Rea ML, Brauner R, Bouligand J, Junier MP, Di Rocco F, Sainte-Rose C et al (2011) Hyperplasia-adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation. Endocr Relat Cancer 18(3):347\u2013356","journal-title":"Endocr Relat Cancer"},{"issue":"2","key":"2031_CR4","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1007\/s12020-016-0930-9","volume":"53","author":"C Ramirez-Renteria","year":"2016","unstructured":"Ramirez-Renteria C, Hernandez-Ramirez LC, Portocarrero-Ortiz L, Vargas G, Melgar V, Espinosa E, Espinosa-de-Los-Monteros AL, Sosa E, Gonzalez B, Zuniga S et al (2016) AIP mutations in young patients with acromegaly and the tampico giant: the Mexican experience. Endocrine 53(2):402\u2013411","journal-title":"Endocrine"},{"key":"2031_CR5","first-page":"1053","volume":"52","author":"JH Briggs","year":"1959","unstructured":"Briggs JH (1959) Acromegaly occurring in one of uniovular twins. Proc R Soc Med 52:1053\u20131054","journal-title":"Proc R Soc Med"},{"issue":"57","key":"2031_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/jnnp.s1-15.57.1","volume":"15","author":"A Lewis","year":"1934","unstructured":"Lewis A (1934) Acromegaly in one of uniovular twins. J Neurol Psychopathol 15(57):1\u201311","journal-title":"J Neurol Psychopathol"},{"issue":"11","key":"2031_CR7","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.2169\/naika.71.1586","volume":"71","author":"T Izumi","year":"1982","unstructured":"Izumi T, Kanazawa Y, Ishibashi M, Yamaji T, Kosaka K (1982) Pituitary gigantism and acromegaly in identical twin brothers. Nippon Naika Gakkai Zasshi 71(11):1586\u20131590","journal-title":"Nippon Naika Gakkai Zasshi"},{"issue":"1","key":"2031_CR8","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1056\/NEJMoa1008020","volume":"364","author":"HS Chahal","year":"2011","unstructured":"Chahal HS, Stals K, Unterlander M, Balding DJ, Thomas MG, Kumar AV, Besser GM, Atkinson AB, Morrison PJ, Howlett TA et al (2011) AIP mutation in pituitary adenomas in the 18th century and today. N Engl J Med 364(1):43\u201350","journal-title":"N Engl J Med"},{"issue":"1","key":"2031_CR9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s12022-022-09703-7","volume":"33","author":"SL Asa","year":"2022","unstructured":"Asa SL, Mete O, Perry A, Osamura RY (2022) Overview of the 2022 WHO classification of pituitary tumors. Endocr Pathol 33(1):6\u201326","journal-title":"Endocr Pathol"},{"issue":"1","key":"2031_CR10","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s00401-013-1084-y","volume":"126","author":"J Trouillas","year":"2013","unstructured":"Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C, Viennet G, Bonneville JF, Assaker R, Auger C, Brue T et al (2013) A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol 126(1):123\u2013135","journal-title":"Acta Neuropathol"},{"issue":"5","key":"2031_CR11","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1210\/jc.2006-2513","volume":"92","author":"AF Daly","year":"2007","unstructured":"Daly AF, Vanbellinghen JF, Khoo SK, Jaffrain-Rea ML, Naves LA, Guitelman MA, Murat A, Emy P, Gimenez-Roqueplo AP, Tamburrano G et al (2007) Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab 92(5):1891\u20131896","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2031_CR12","doi-asserted-by":"publisher","first-page":"E1242","DOI":"10.1210\/jc.2015-1869","volume":"100","author":"LC Hernandez-Ramirez","year":"2015","unstructured":"Hernandez-Ramirez LC, Gabrovska P, Denes J, Stals K, Trivellin G, Tilley D, Ferrau F, Evanson J, Ellard S, Grossman AB et al (2015) Landscape of familial isolated and young-onset pituitary adenomas: prospective diagnosis in aip mutation carriers. J Clin Endocrinol Metab 100(9):E1242\u2013E1254","journal-title":"J Clin Endocrinol Metab"},{"key":"2031_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.841118","volume":"13","author":"G Giuffrida","year":"2022","unstructured":"Giuffrida G, D\u2019Argenio V, Ferrau F, Lasorsa VA, Polito F, Aliquo F, Ragonese M, Cotta OR, Alessi Y, Oteri R et al (2022) Methylome analysis in nonfunctioning and GH-secreting pituitary adenomas. Front Endocrinol (Lausanne) 13:841118","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"7","key":"2031_CR14","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s40618-018-0988-8","volume":"42","author":"F Ferrau","year":"2019","unstructured":"Ferrau F, Romeo PD, Puglisi S, Ragonese M, Spagnolo F, Salpietro C, Ientile R, Curro M, Visalli G, Alibrandi A et al (2019) GSTP1 gene methylation and AHR rs2066853 variant predict resistance to first generation somatostatin analogs in patients with acromegaly. J Endocrinol Invest 42(7):825\u2013831","journal-title":"J Endocrinol Invest"},{"issue":"2","key":"2031_CR15","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1210\/er.2012-1013","volume":"34","author":"A Beckers","year":"2013","unstructured":"Beckers A, Aaltonen LA, Daly AF, Karhu A (2013) Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr Rev 34(2):239\u2013277","journal-title":"Endocr Rev"},{"issue":"6","key":"2031_CR16","doi-asserted-by":"publisher","first-page":"e2247","DOI":"10.1210\/clinem\/dgaa040","volume":"105","author":"P Marques","year":"2020","unstructured":"Marques P, Caimari F, Hernandez-Ramirez LC, Collier D, Iacovazzo D, Ronaldson A, Magid K, Lim CT, Stals K, Ellard S et al (2020) Significant Benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors. J Clin Endocrinol Metab 105(6):e2247\u2013e2260","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Journal of Endocrinological Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-023-02031-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40618-023-02031-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-023-02031-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T10:25:37Z","timestamp":1689330337000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40618-023-02031-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,9]]},"references-count":16,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["2031"],"URL":"https:\/\/doi.org\/10.1007\/s40618-023-02031-5","relation":{},"ISSN":["1720-8386"],"issn-type":[{"value":"1720-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,9]]},"assertion":[{"value":"28 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by the local ethics committee of the University Hospital of W\u00fcrzburg (Approval number 85\/12) and carried out in compliance with the declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"The patients\/participants provided written informed consent to provide their data in this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}