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The DAX-1 protein (encoded by <jats:italic>NR0B1<\/jats:italic>) is a vertebrate-specific orphan nuclear receptor and is also a transcriptional factor for adrenal and reproductive development. CAH usually causes adrenal insufficiency in infancy and early childhood, leading to hypogonadotropic hypogonadism in adulthood; however, few adult cases have been reported to date. In this study, we examined a Chinese family with one adult patient with CAH, and identified a putative variant of <jats:italic>NR0B1<\/jats:italic> gene via next-generation sequencing (NGS), which was confirmed with Sanger sequencing. A novel nonsense variant (c.265C&gt;T) was identified in the <jats:italic>NR0B1<\/jats:italic> gene, which caused the premature termination of DAX-1 at residue 89 (p.G89*). Furthermore, mutant <jats:italic>NR0B1<\/jats:italic> gene displayed a partial DAX-1 function, which may explain the late pathogenesis in our case. Additionally, qPCR revealed the abnormal expression of four important genes identified from ChIP-seq, which were associated with energy homeostasis and steroidogenesis, and were influenced by the DAX-1 mutant. In addition, hormone disorders can be caused by DAX-1 mutant and partially recovered by siRNA of <jats:italic>PPARGC1A<\/jats:italic>. Herein, we identified a novel nonsense variant (c.265C&gt;T) of <jats:italic>NR0B1<\/jats:italic> in a 24-year-old Chinese male who was suffering from CAH. This mutant DAX-1 protein was found to have disordered energy homeostasis and steroidogenesis based on in vitro studies, which was clinically consistent with the patient\u2019s phenotypic features.<\/jats:p>","DOI":"10.1038\/s41598-021-95642-y","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T10:10:36Z","timestamp":1628503836000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia"],"prefix":"10.1038","volume":"11","author":[{"given":"Da-Bei","family":"Fan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao-Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"95642_CR1","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1056\/NEJMra021561","volume":"349","author":"PW Speiser","year":"2003","unstructured":"Speiser, P. 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