{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T23:50:12Z","timestamp":1769730612511,"version":"3.49.0"},"reference-count":29,"publisher":"Endocrinology Research Centre","issue":"5","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p>\n                    <jats:bold>INTRODUCTION.<\/jats:bold>\n                    Among the disorders of sex development (DSD) with karyotype 46,XY, there is a group of diseases caused by defects of androgen synthesis. The last stage of in the synthesis of androgens is the conversion of testosterone into a more active androgen dihydrotestosterone, which occurs under the influence of the enzyme 5\u03b1-reductase type II (SRD5A2). SRD5A2 deficiency is a rare disease with autosomal recessive inheritance.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>AIM.<\/jats:bold>\n                    To give a clinical and molecular genetic characterization of 14 new cases with confirmed molecular diagnosis of SRD5A2 deficiency, as well as 4 cases of DSD 46,XY, where monoallelic changes in the\n                    <jats:italic>SRD5A2<\/jats:italic>\n                    gene were detected.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>MATERIALS AND METHODS.<\/jats:bold>\n                    The study included 310 patients with DSD 46,XY. Molecular genetic analysis was performed using the NGS method using a targeted panel for multiplex amplification and subsequent sequencing of the coding regions of the following genes:\n                    <jats:italic>AKR1C2, AKR1C4, AMH, AMHR2, AR, ARX, ATRX, CBX2, CYB5A, CYP11A1, CYP17A1, DHCR7, DHH, EMX2,<\/jats:italic>\n                    <jats:italic>ESR2, FGD1, FGF9, FGFR2, FKBP4, FOXF2, FOXL2, HOXA13, HSD17B3, HSD3B2, ICK, LHCGR, LHX1, LHX9, MAMLD1, MAP3K1, MID1, NR0B1, NR5A1, POR, PTGDS, SOX9, SRD5A2, SRY, STAR, SUPT3H, TSPYL1, WNT4, WT1, ZFPM2.<\/jats:italic>\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    By molecular genetic analysis 16 different variants were identified in the\n                    <jats:italic>SRD5A2<\/jats:italic>\n                    gene (2 in several families), 4 of which had not been previously described.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    The study highlights the importance of molecular genetic analysis in the differential diagnosis of DSD 46,XY.\n                  <\/jats:p>","DOI":"10.14341\/probl13544","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T08:51:37Z","timestamp":1764838297000},"page":"40-46","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":0,"title":["Clinical, hormonal and molecular genetic characteristics of 18 cases of disorders of sex development (DSD) 46,XY associated with variants in the SRD5A2 gene"],"prefix":"10.14341","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2000-7694","authenticated-orcid":true,"given":"N. Y.","family":"Kalinchenko","sequence":"first","affiliation":[{"name":"Endocrinology Research Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0412-7140","authenticated-orcid":true,"given":"N. A.","family":"Makretskaya","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-5372","authenticated-orcid":true,"given":"A. A.","family":"Kolodkina","sequence":"additional","affiliation":[{"name":"Endocrinology Research Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1320-6561","authenticated-orcid":true,"given":"M. A.","family":"Kareva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-4841","authenticated-orcid":true,"given":"A. N.","family":"Tiulpakov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Hughes IA, Houk C, Ahmed SF, Lee PA; LWPES Consensus Group; ESPE Consensus Group. Consensus statement on management of intersex disorders. Arch Dis Child. 2006;91(7):554-63. doi: https:\/\/doi.org\/10.1136\/adc.2006.098319","DOI":"10.1136\/adc.2006.098319"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Cools M, Nordenstr\u00f6m A, Robeva R, Hall J, et al. COST Action BM1303 working group 1. Caring for individuals with a difference of sex development (DSD): Consensus Statement. Nat Rev Endocrinol. 2018;14(7):415-429. doi: https:\/\/doi.org\/10.1038\/s41574-018-0010-8","DOI":"10.1038\/s41574-018-0010-8"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Thigpen AE, Silver RI, Guileyardo JM, Casey ML, McConnell JD, Russell DW. Tissue distribution and ontogeny of steroid 5 alphareductase isozyme expression. J Clin Invest. 1993;92(2):903-10. doi: https:\/\/doi.org\/10.1172\/JCI116665","DOI":"10.1172\/JCI116665"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Geissler WM, Davis DL, Wu L, Bradshaw KD, Patel S, et al. Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3. Nat Genet. 1994;7(1):34-9. doi: https:\/\/doi.org\/10.1038\/ng0594-34.","DOI":"10.1038\/ng0594-34"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Kalinchenko N.Yu., Kolodkina A.A., Raigorodskaya N.Yu., Tyulpakov A.N. Clinical and molecular genetic characteristics of patients with disorder of sex development 46,XY caused by mutations in the NR5A1 gene. \/\/ Problems of Endocrinology. - 2020. - Vol. 66. - No. 3. - P. 62-69. doi: https:\/\/doi.org\/10.14341\/probl12445","DOI":"10.14341\/probl12445"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Kolodkina A.A., Karmanov M.E., Kalinchenko N.Yu., Nizhnik A.N., Nokel M.A., et al. Clinical, hormonal and molecular genetic characteristics of three cases of 46XY sex development disorder caused by 5\u03b1-reductase type II deficiency. \/\/ Problems of Endocrinology. - 2010. - Vol. 56. - No. 3. - P. 34-40. doi: https:\/\/doi.org\/10.14341\/probl201056334-40.","DOI":"10.14341\/probl201056334-40"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24. doi: https:\/\/doi.org\/10.1038\/gim.2015.30","DOI":"10.1038\/gim.2015.30"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Ryzhkova OP, Kardymon OL, Prokhorchuk EB, et al. Guidelines for the interpretation of human DNA sequence data obtained by massively parallel sequencing (MPS) methods (2018 edition, version 2). \/\/ Medical Genetics. - 2019. - Vol. 18. - No. 2. doi: https:\/\/doi.org\/10.25557\/2073-7998.2019.02.3-23","DOI":"10.25557\/2073-7998.2019.02.3-23"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"De Vaal OM. Genital intersexuality in three brothers, connected with consanguineous marriages in the three previous generations. Acta Paediat. 44: 35-39, 1955","DOI":"10.1111\/j.1651-2227.1955.tb04110.x"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Walsh PC, Madden JD, Harrod MJ, et al. Familial incomplete male pseudohermaphroditism type 2: Decreased dihydrotestosterone formation in pseudovaginal perineo-scrotal hypospadias. New Engl J Med 291:944, 1974","DOI":"10.1056\/NEJM197410312911806"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE. Steroid 5alpha- reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science. 1974;186(4170):1213-5. doi: https:\/\/doi.org\/10.1126\/science.186.4170.1213","DOI":"10.1126\/science.186.4170.1213"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Andersson S, Berman DM, Jenkins EP, Russell DW. Deletion of steroid 5 alpha- reductase 2 gene in male pseudohermaphroditism. Nature. 1991;354(6349):159-61. doi: https:\/\/doi.org\/10.1038\/354159a0","DOI":"10.1038\/354159a0"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Thigpen AE, Davis DL, Gautier T et al. Brief report: the molecular basis of steroid 5 alpha-reductase deficiency in a large Dominican kindred. N Engl J Med. 1992;327(17):1216-9. doi: https:\/\/doi.org\/10.1056\/NEJM199210223271706","DOI":"10.1056\/NEJM199210223271706"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Thigpen AE, Davis DL, Milatovich A, Mendonca BB, ImperatoMcGinley J, et al. Molecular genetics of steroid 5 alphareductase 2 deficiency. J Clin Invest. 1992;90(3):799-809. doi: https:\/\/doi.org\/10.1172\/JCI115954","DOI":"10.1172\/JCI115954"},{"key":"ref15","unstructured":"Song YN, Fan LJ, Zhao X, Gong CX. [Clinical phenotype and gene analysis of 86 cases of 5 alpha reductase deficiency]. Zhonghua Er Ke Za Zhi. 2019;57(2):131-135. Chinese. doi: https:\/\/doi.org\/10.3760\/cma.j.issn.0578-1310.2019.02.013"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Ko JM, Cheon CK, Kim GH, Kim SH, Kim KS, Yoo HW. Clinical characterization and analysis of the SRD5A2 gene in six Korean patients with 5alpha-reductase type 2 deficiency. Horm Res Paediatr. 2010;73(1):41-8. doi: https:\/\/doi.org\/10.1159\/000271915","DOI":"10.1159\/000271915"},{"key":"ref17","unstructured":"Chan AO, But BW, Lau GT, Lam AL, Ng KL, Lam YY, Lee CY, Shek CC. Diagnosis of 5alpha-reductase 2 deficiency: a local experience. Hong Kong Med J. 2009;15(2):130-5"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Wilson JD, Griffin JE, Russell DW. Steroid 5 alphareductase 2 deficiency. Endocr Rev. 1993;14(5):577-93. doi: https:\/\/doi.org\/10.1210\/edrv-14-5-577","DOI":"10.1210\/edrv-14-5-577"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Di Marco C, Bulotta AL, Varetti C, Dosa L, Michelucci A, etal. Ambiguous external genitalia due to defect of 5-\u03b1-reductase in seven Iraqi patients: prevalence of a novel mutation. Gene. 2013;526(2):490-3. doi: https:\/\/doi.org\/10.1016\/j.gene.2013.04.070","DOI":"10.1016\/j.gene.2013.04.070"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Parlak M, Durmaz E, Gursoy S, Bircan I, Akcurin S. Try235Phe homozygous mutation of the steroid 5-a reductase type 2 (SRD5A2) gene in a Turkish patient. Ann Saudi Med. 2014;34(3):254-6. doi: https:\/\/doi.org\/10.5144\/0256-4947.2014.254","DOI":"10.5144\/0256-4947.2014.254"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Hiort O, Sch\u00fctt SM, Bals-Pratsch M, Holterhus PM, Marschke C, Struve D. A novel homozygous disruptive mutation in the SRD5A2-gene in a partially virilized patient with 5alpha-reductase deficiency. Int J Androl. 2002;25(1):55-8. doi: https:\/\/doi.org\/10.1046\/j.1365-2605.2002.00325.x","DOI":"10.1046\/j.1365-2605.2002.00325.x"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Cheng T, Wang H, Han B, Zhu H et al. Identification of three novel SRD5A2 mutations in Chinese patients with 5\u03b1-reductase 2 deficiency. Asian J Androl. 2019;21(6):577-581. doi: https:\/\/doi.org\/10.4103\/aja.aja_113_18","DOI":"10.4103\/aja.aja_113_18"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Skordis N, Patsalis PC, Bacopoulou I, Sismani C, Sultan C, Lumbroso S. 5alpha-reductase 2 gene mutations in three unrelated patients of Greek Cypriot origin: identification of an ancestral founder effect. J Pediatr Endocrinol Metab. 2005;18(3):241-6. doi: https:\/\/doi.org\/10.1515\/jpem.2005.18.3.241","DOI":"10.1515\/JPEM.2005.18.3.241"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Makretskaya N, Nanzanova U, Kalinchenko N, Hamaganova I, Eremina E, et al. High carrier frequency of a splicing c.589G>A variant in the SRD5A2 gene among Buryats. Horm Res Paediatr. 2023;96(suppl 4):1\u2013643 61st Annual Meeting of the ESPE doi: https:\/\/doi.org\/10.1159\/000533803; P1-577","DOI":"10.1159\/000533803"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Arya S, Tiwari A, Lila AR, Sarathi V, Bhandare VV, Kumbhar BV et al. Homozygous p.Val89Leu plays an important pathogenic role in 5\u03b1-reductase type 2 deficiency patients with homozygous p.Arg246Gln in SRD5A2. Eur J Endocrinol. 2020;183(3):275-284. doi: doi: https:\/\/doi.org\/10.1530\/EJE-19-1050","DOI":"10.1530\/EJE-19-1050"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Abac\u0131 A, \u00c7atl\u0131 G, K\u0131rb\u0131y\u0131k \u00d6, \u015eahin NM, Abal\u0131 ZY et al. Genotypephenotype correlation, gonadal malignancy risk, gender preference, and testosterone\/dihydrotestosterone ratio in steroid 5-alpha-reductase type 2 deficiency: a multicenter study from Turkey. J Endocrinol Invest. 2019;42(4):453-470. doi: https:\/\/doi.org\/10.1007\/s40618-018-0940-y","DOI":"10.1007\/s40618-018-0940-y"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Nordenskj\u00f6ld A, Ivarsson SA. Molecular characterization of 5 alpha-reductase type 2 deficiency and fertility in a Swedish family. J Clin Endocrinol Metab. 1998;83(9):3236-8. doi: https:\/\/doi.org\/10.1210\/jcem.83.9.5125","DOI":"10.1210\/jcem.83.9.5125"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Maimoun L, Philibert P, Cammas B, Audran F, et al. Phenotypical, biological, and molecular heterogeneity of 5\u03b1-reductase deficiency: an extensive international experience of 55 patients. J Clin Endocrinol Metab. 2011;96(2):296-307. doi: https:\/\/doi.org\/10.1210\/jc.2010-1024.","DOI":"10.1210\/jc.2010-1024"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Walter KN, Kienzle FB, Frankenschmidt A, Hiort O. et al. Difficulties in diagnosis and treatment of 5alpha-reductase type 2 deficiency in a newborn with 46,XY DSD. Horm Res Paediatr. 2010;74(1):67-71. doi: https:\/\/doi.org\/10.1159\/000313372","DOI":"10.1159\/000313372"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/13544\/10911","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T11:40:22Z","timestamp":1769686822000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/13544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,12,2]]}},"URL":"https:\/\/doi.org\/10.14341\/probl13544","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"value":"2308-1430","type":"electronic"},{"value":"0375-9660","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12,2]]}}}