{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:23:27Z","timestamp":1791239007487,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,26]],"date-time":"2020-07-26T00:00:00Z","timestamp":1595721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009331","name":"Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support","doi-asserted-by":"publisher","award":["ZYLX201821"],"award-info":[{"award-number":["ZYLX201821"]}],"id":[{"id":"10.13039\/501100009331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with steroid 5\u03b1\u2010reductase 2 deficiency (5\u03b1\u2010RD) caused by <jats:italic>SRD5A2<\/jats:italic> (OMIM #607306) variants present variable genotypes and phenotypes. The genotype\u2010phenotype correlations remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated genotype\u2010phenotype correlations of <jats:italic>SRD5A2<\/jats:italic> variants in a large Chinese single\u2010center cohort. Phenotypes were categorized using the external masculinization score (EMS), urethral meatus and gonad position, and penile length\u2010standard deviation score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 130 included patients, 113 had hypospadias, and 17 had a normal urethral meatus position. Testosterone\/dihydrotestosterone (T\/DHT) values were not significantly associated with phenotypic severity (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.539\u20130.989). Of the 31 <jats:italic>SRD5A2<\/jats:italic> variants, including 10 novel variants, p.R227Q was the most prevalent (39.62%), followed by p.Q6* (16.92%), p.R246Q (13.46%), and p.G203S (10.38%). Compared to biallelic missense mutations, biallelic nonsense mutations were associated with a lower EMS and urethral meatus score (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.009 and <jats:italic>p<\/jats:italic>\u00a0=\u00a00.024, respectively). Patients homozygous for p.R227Q exhibited mild and variable phenotypes, while those homozygous for p.Q6*, p.R246Q, or p.G203S showed consistently severe phenotypes. The phenotypes were variable and milder in patients with compound heterozygosity for p.R227Q and these mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>T\/DHT does not predict phenotype severity. The most prevalent <jats:italic>SRD5A2<\/jats:italic> variant in Han Chinese is p.R227Q, which is associated with milder phenotypes and greater phenotypic variability. <jats:italic>SRD5A2<\/jats:italic> variants may significantly influence phenotypic variation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1431","type":"journal-article","created":{"date-parts":[[2020,7,26]],"date-time":"2020-07-26T07:39:00Z","timestamp":1595749140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Clinical characteristics and genotype\u2010phenotype correlations of 130 Chinese children in a high\u2010homogeneity single\u2010center cohort with 5\u03b1\u2010reductase 2 deficiency"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6257-3395","authenticated-orcid":false,"given":"Lijun","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Genetics, Metabolism Beijing 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d'endocrinologie, gyn\u00e9cologie et diab\u00e9tologiep\u00e9diatriques H\u00f4pitaluniversitaire Necker Enfants Malades universit\u00e9 de Paris IMAGINE institute Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-6810","authenticated-orcid":false,"given":"Lele","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics, Metabolism Beijing Children\u2019s Hospital Capital Medical University National Center for Children\u2019s Health Beijing China"},{"name":"Beijing Key Laboratory for Genetics of Birth Defects Beijing Children\u2019s Hospital Capital Medical University National Center for Children\u2019s Health Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics, Metabolism Beijing Children\u2019s Hospital Capital Medical University National Center 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