{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:00:10Z","timestamp":1790312410305,"version":"4.1.0"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      5\u03b1-Reductase type 2 deficiency (5\u03b1-RD2) is an autosomal recessive differences\/disorders of sex development caused by\n                      <jats:italic>SRD5A2<\/jats:italic>\n                      gene mutations, characterized by impaired testosterone-to-dihydrotestosterone conversion and highly heterogeneous clinical phenotypes. The genotype-phenotype correlation of 5\u03b1-RD2 remains incompletely understood, and large-scale multicenter evidence is lacking for clinical management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Embase, CNKI, Wanfang, and Chinese Medical Journals databases from inception to December 2025.\u00a0A total of 279 genetically confirmed patients with 5\u03b1-RD2 from 36 countries (64.77% from Asia) were included. Demographic, clinical, biochemical, genetic, and prognostic data were extracted and analyzed using SPSS 25.0.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventy-eight pathogenic\n                      <jats:italic>SRD5A2<\/jats:italic>\n                      mutations were identified, with missense mutations being the most common (64.10%) and p.R246Q the most prevalent variant. The mutation spectrum showed significant geographic heterogeneity. Consanguinity was strongly associated with homozygous mutations (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001), and patients with homozygous mutations had significantly more severe undermasculinization than compound heterozygotes (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.011). p.R246Q, p.G203S, and p.R246W were significantly associated with a higher likelihood of hypospadias; p.R227Q was significantly associated with a lower likelihood of cryptorchidism and scrotal abnormalities. Frameshift mutations were associated with impaired pubertal development (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.013). Homozygous carriers were diagnosed significantly later than heterozygotes (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.029), and serum FSH levels positively correlated with phenotypic severity (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.021).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We verified that the genotype\u2013phenotype correspondence is non-linear and multifactorial, jointly modulated by mutation subtype, residual enzyme activity, endocrine axis status, geographical disparities, consanguinity, and regional medical resource availability. These findings provide more reliable evidence for clinical diagnosis, treatment, and prognosis assessment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1919643","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:27:43Z","timestamp":1790310463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical characteristics and genotype\u2013phenotype correlation analysis in 279 patients with 5\u03b1-reductase type 2 deficiency"],"prefix":"10.3389","volume":"17","author":[{"given":"Kun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabology, Liaocheng People\u2019s Hospital","place":["Liaocheng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabology, Liaocheng People\u2019s Hospital Affiliated to Shandong First Medical University","place":["Liaocheng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabology, Liaocheng People\u2019s Hospital","place":["Liaocheng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabology, Liaocheng People\u2019s Hospital","place":["Liaocheng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabology, Liaocheng People\u2019s Hospital","place":["Liaocheng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabology, Liaocheng People\u2019s Hospital","place":["Liaocheng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7551\/mitpress\/7458.003.0020","article-title":"Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism","volume":"186","author":"Imperato-McGinley","year":"1974","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/nejm197410312911806","article-title":"Familial incomplete male pseudohermaphroditism, type 2. 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