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The aim of this study was to determine the frequency of <jats:italic>AIP<\/jats:italic> germline mutations in patients with young-onset sporadic pituitary macroadenomas.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The <jats:italic>AIP<\/jats:italic> gene was sequenced in 218 Portuguese patients with sporadic pituitary macroadenomas diagnosed before the age of 40\u00a0years.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Heterozygous rare sequence variants in <jats:italic>AIP<\/jats:italic> were identified in 18 (8.3%) patients. However, only four (1.8%) patients had pathogenic or likely pathogenic variants. These consisted of two already known mutations (p.Arg81* and p.Leu115Trpfs*41) and two novel mutations (p.Glu246*, p.Ser53Thrfs*36). All four patients had GH-secreting adenomas diagnosed between the ages of 14 and 25\u00a0years. The frequency of <jats:italic>AIP<\/jats:italic> pathogenic or likely pathogenic variants in patients under the age of 30 and 18\u00a0years was 3.4% and 5.0%, respectively.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The frequency of <jats:italic>AIP<\/jats:italic> mutations in this cohort was lower than in other studies. Previous reports may have overestimated the contribution of <jats:italic>AIP<\/jats:italic> mutations due to the inclusion of genetic variants of uncertain significance. The identification of novel <jats:italic>AIP<\/jats:italic> mutations expands the known spectrum of genetic causes of pituitary adenomas and may help understand the role of <jats:italic>AIP<\/jats:italic> mutations in the molecular mechanisms underlying pituitary tumorigenesis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s40618-023-02083-7","type":"journal-article","created":{"date-parts":[[2023,5,7]],"date-time":"2023-05-07T03:13:32Z","timestamp":1683429212000},"page":"2299-2307","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Low frequency of AIP mutations in patients with young-onset sporadic pituitary macroadenomas"],"prefix":"10.1007","volume":"46","author":[{"given":"L. M.","family":"Gaspar","sequence":"first","affiliation":[]},{"given":"C. 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