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AHC is caused by a mutation in the <jats:italic>DAX-1<\/jats:italic> gene (<jats:italic>NR0B1<\/jats:italic>). More commonly, this disease is characterized by early-onset PAI, with symptoms in the first months of life. However, a less severe phenotype termed late-onset AHC has been described, as PAI signs and symptoms may begin in adolescence and adulthood. Here we describe a family report of a novel mutation within <jats:italic>NR0B1<\/jats:italic> gene and variable reproductive phenotypes, including spontaneous fertility, in a very late-onset X-linked AHC kindred.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>Three affected maternal male relatives had confirmed PAI diagnosis between 30 y and at late 64 y. The X-linked pattern has made the endocrinology team to AHC suspicion. Regarding the HPG axis, all males presented a distinct degree of testosterone deficiency and fertility phenotypes, varying from a variable degree of hypogonadism, oligoasthenoteratozoospermia to spontaneous fertility. Interestingly, the other five maternal male relatives unexpectedly died during early adulthood, most likely due to undiagnosed PAI\/adrenal crisis as the probable cause of their premature deaths. Sequencing analysis of the <jats:italic>NR0B1<\/jats:italic> gene has shown a novel <jats:italic>NR0B1<\/jats:italic> mutation (p.Tyr378Cys) that segregated in three AHC family members.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p><jats:italic>NR0B1<\/jats:italic> p.Tyr378Cys segregates in an AHC family with a variable degree of adrenal and gonadal phenotypes, and its hemizygous trait explains the disease in affected family members. We recommend that <jats:italic>NR0B1<\/jats:italic> mutation carriers, even those that are allegedly asymptomatic, be carefully monitored while reinforcing education to prevent PAI and consider early sperm banking when spermatogenesis still viable.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12902-020-0500-2","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T13:22:56Z","timestamp":1583500976000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Spontaneous fertility and variable spectrum of reproductive phenotype in a family with adult-onset X-linked adrenal insufficiency harboring a novel DAX-1\/NR0B1 mutation"],"prefix":"10.1186","volume":"20","author":[{"given":"Michelle Cerutti C.","family":"Vargas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe Scipi\u00e3o","family":"Moura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cec\u00edlia P.","family":"Elias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara R.","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"Rassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilda S.","family":"Kunii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-966X","authenticated-orcid":false,"given":"Magnus R.","family":"Dias-da-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia Amanda","family":"Costa-Barbosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,6]]},"reference":[{"issue":"1\u20132","key":"500_CR1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.mce.2011.04.017","volume":"346","author":"U Jadhav","year":"2011","unstructured":"Jadhav U, Harris RM, Jameson JL. 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A copy of written consent is available for review by the journal editor.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21"}}