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It is caused by defects in the<jats:italic>HSD11B2<\/jats:italic>gene, encoding the enzyme 11\u03b2-hydroxysteroid dehydrogenase type 2 (11\u03b2-HSD2), which is primarily involved in the peripheral conversion of cortisol to cortisone. To date, over 50 deleterious<jats:italic>HSD11B2<\/jats:italic>mutations have been identified worldwide. Multiple molecular mechanisms function in the lowering of 11\u03b2-HSD2 activity, including damaging protein stability, lowered affinity for the substrate and cofactor, and disrupting the dimer interface. Genetic polymorphism, environmental factors as well as epigenetic modifications may also offer an implicit explanation for the molecular pathogenesis of AME. A precise diagnosis depends on genetic testing, which allows for early and specific management to avoid the morbidity and mortality from target organ damage. In this review, we provide insights into the molecular genetics of classic and non-classic apparent mineralocorticoid excess and aim to offer a comprehensive overview of this monogenic disease.<\/jats:p>","DOI":"10.1186\/s12967-022-03698-9","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T11:07:34Z","timestamp":1667473654000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Apparent mineralocorticoid excess: comprehensive overview of molecular genetics"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4335-3343","authenticated-orcid":false,"given":"Yi-ting","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong-yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-ming","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-qi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-liang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"3698_CR1","unstructured":"Werder E, et al., Unusual steroid excretion in a child with low renin hypertension. 1974. 6: p.\u00a0385\u2013389."},{"issue":"5","key":"3698_CR2","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1210\/jcem-44-5-924","volume":"44","author":"MI New","year":"1977","unstructured":"New MI, et al. 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