{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T10:08:10Z","timestamp":1789207690093,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":254,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010382","name":"European Society of Endocrinology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015652","name":"Barts Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015652","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Familial isolated pituitary adenoma (FIPA) accounts for approximately 2%\u20135% of all pituitary adenomas, with inactivating variants of the aryl hydrocarbon receptor\u2010interacting protein (\n                    <jats:italic>AIP<\/jats:italic>\n                    ) gene representing the most frequent known genetic cause. Clinically, patients with\n                    <jats:italic>AIP<\/jats:italic>\n                    variants often have young\u2010onset macroadenomas with growth hormone hypersecretion, although disease severity and penetrance are variable. Most reported\n                    <jats:italic>AIP<\/jats:italic>\n                    variants are point mutations, whereas large deletions are rare and potentially underdiagnosed. Accurate detection of\n                    <jats:italic>AIP<\/jats:italic>\n                    copy\u2010number variants requires methods such as multiplex ligation\u2010dependent probe amplification or validated copy\u2010number analysis of next\u2010generation sequencing data, as Sanger sequencing alone may fail to identify these alterations. Due to the rarity of the disease, it is unknown whether large deletions in the ubiquitously expressed\n                    <jats:italic>AIP<\/jats:italic>\n                    gene are associated with potentially more severe phenotype. Available data suggest that large deletions may occur in 8%\u201310% of\n                    <jats:italic>AIP<\/jats:italic>\n                    mutation\u2010positive pedigrees, highlighting the importance of incorporating copy\u2010number variant detection into\n                    <jats:italic>AIP<\/jats:italic>\n                    testing workflows. We analysed data from all published patients with large\n                    <jats:italic>AIP<\/jats:italic>\n                    deletions (\n                    <jats:italic>n<\/jats:italic>\n                    = 25) and report here two novel large\n                    <jats:italic>AIP<\/jats:italic>\n                    deletions (Exons 3\u20134 and Exons 2\u20136 deletions) and three additional three families, including an Albanian kindred associated with metastatic H\u00fcrthle cell thyroid carcinoma. No major differences compared with other\n                    <jats:italic>AIP<\/jats:italic>\n                    variants were found in age at diagnosis, tumour size, hormonal profile, sex distribution or presence of other tumours. A role for\n                    <jats:italic>AIP<\/jats:italic>\n                    variants in thyroid carcinogenesis is unlikely.\n                  <\/jats:p>","DOI":"10.1155\/humu\/4212742","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:40:56Z","timestamp":1789206056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Genetic Spectrum of Large AIP Deletions"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3303-6530","authenticated-orcid":false,"given":"Tea 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Alexandros","family":"Drakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1155-276X","authenticated-orcid":false,"given":"Kesson","family":"Magid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5638-3918","authenticated-orcid":false,"given":"Thomas O.","family":"Millner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6730-6109","authenticated-orcid":false,"given":"Robert 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