{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:38:35Z","timestamp":1784864315707,"version":"3.55.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 81860516"],"award-info":[{"award-number":["No. 81860516"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Xingtai Science and Technology Bureau","award":["2020ZC343"],"award-info":[{"award-number":["2020ZC343"]}]},{"name":"Science and Technology Foundation of Guizhou Health Committee","award":["gzwjkj2019-1-036"],"award-info":[{"award-number":["gzwjkj2019-1-036"]}]},{"name":"National Natural Science Fund Cultivation Project of Guizhou Medical University","award":["20NSP025"],"award-info":[{"award-number":["20NSP025"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Over 100 mutations in the <jats:italic>SRD5A2<\/jats:italic> gene have been identified in subjects with 46,XY disorder of sex development (DSD). Exploration of <jats:italic>SRD5A2<\/jats:italic> mutations and elucidation of the molecular mechanisms behind their effects should reveal the functions of the domains of the 5\u03b1-reductase 2 enzyme and identify the cause of 46,XY DSD. Previously, we reported a novel compound heterozygous p.Q6X\/p.H232R mutation of the <jats:italic>SRD5A2<\/jats:italic> gene in a case with 46,XY DSD. Whether the compound heterozygous p.Q6X\/p.H232R mutation in this gene causes 46,XY DSD requires further exploration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The two 46,XY DSD cases were identified and sequenced. In order to identify the source of the compound heterozygous p.Q6X\/p.H232R mutation, the parents, maternal grandparents, and maternal uncle were sequenced. Since p.Q6X mutation is a nonsense mutation, p.H232R mutation was transfected into HEK293 cells and dihydrotestosterone (DHT) production were analyzed by liquid chromatography\u2013mass spectrometry (LC\u2013MS) for 5\u03b1-reductase 2 enzyme activities test. Apparent michaelis constant (Km) were measured of p.H232R mutation to analyze the binding ability change of 5\u03b1-reductase 2 enzyme with testosterone (T) or NADPH.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The sequence results showed that the two 46,XY DSD cases were the compound heterozygous p.Q6X\/p.H232R mutation, of which the heterozygous p.Q6X mutation originating from maternal family and heterozygous p.H232R mutation originating from the paternal family. The function analysis confirmed that p.H232R variant decreased the DHT production by LC\u2013MS test. The Km analysis demonstrated that p.H232R mutation affected the binding of <jats:italic>SRD5A2<\/jats:italic> with T or NADPH.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings confirmed that the compound heterozygous p.Q6X\/p.H232R mutation in the <jats:italic>SRD5A2<\/jats:italic> gene is the cause of 46,XY DSD. p.H232R mutation reduced DHT production while attenuating the catalytic efficiency of the 5\u03b1-reductase 2 enzyme.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13052-022-01243-4","type":"journal-article","created":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T23:02:50Z","timestamp":1648162970000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mutational analysis of compound heterozygous mutation p.Q6X\/p.H232R in SRD5A2 causing 46,XY disorder of sex development"],"prefix":"10.1186","volume":"48","author":[{"given":"Liwei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirui","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongqian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingsheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5060-787X","authenticated-orcid":false,"given":"Hui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,24]]},"reference":[{"issue":"4","key":"1243_CR1","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1210\/jc.2017-01888","volume":"103","author":"A Berglund","year":"2018","unstructured":"Berglund A, Johannsen TH, Stochholm K, Viuff MH, Fedder J, Main KM, et al. 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