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Review

Integrative and Analytical Review of the 5-Alpha-Reductase Type 2 Deficiency Worldwide

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Pages 83-96 | Published online: 14 Apr 2020

References

  • Nowakowski H, Lenz W. Genetic aspects in male hypogonadism. Recent Prog Horm Res. 1961;17:53–95.
  • Imperato-McGinley J, Zhu YS. Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. Mol Cell Endocrinol. 2002;198(1–2):51–59. doi:10.1016/S0303-7207(02)00368-4
  • 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):1213–1215. doi:10.1126/science.186.4170.1213
  • Walsh PC, Madden JD, Harrod MJ, Goldstein JL, MacDonald PC, Wilson JD. Familial incomplete male pseudohermaphroditism, type 2. Decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med. 1974;291(18):944–949. doi:10.1056/NEJM197410312911806
  • Mendonca BB, Inacio M, Costa EM, et al. Male pseudohermaphroditism due to steroid 5alpha-reductase 2 deficiency. Diagnosis, psychological evaluation, and management. Medicine (Baltimore). 1996;75(2):64–76. doi:10.1097/00005792-199603000-00003
  • Thigpen AE, Davis DL, Milatovich A, et al. Molecular genetics of steroid 5 alpha-reductase 2 deficiency. J Clin Invest. 1992;90(3):799–809. doi:10.1172/JCI115954
  • Maimoun L, Philibert P, Cammas B, et al. Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients. J Clin Endocrinol Metab. 2011;96(2):296–307. doi:10.1210/jc.2010-1024
  • Andonova S, Robeva R, Vazharova R, et al. New territory for an old disease: 5-alpha-reductase type 2 deficiency in Bulgaria. Sex Dev. 2017;11(1):21–28. doi:10.1159/000454974
  • Sinnecker GH, Hiort O, Dibbelt L, et al. Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency. Am J Med Genet. 1996;63(1):223–230. doi:10.1002/(SICI)1096-8628(19960503)63:1<223::AID-AJMG39>3.0.CO;2-O
  • Kolesinska Z, Ahmed SF, Niedziela M, et al. Changes over time in sex assignment for disorders of sex development. Pediatrics. 2014;134(3):e710–e715. doi:10.1542/peds.2014-1088
  • Atta I, Ibrahim M, Parkash A, Lone SW, Khan YN, Raza J. Etiological diagnosis of undervirilized male/XY disorder of sex development. J Coll Physicians Surg Pak. 2014;24(10):714–718. doi:10.2014/JCPSP.714718
  • Achermann JC, Domenice S, Bachega TA, Nishi MY, Mendonca BB. Disorders of sex development: effect of molecular diagnostics. Nat Rev Endocrinol. 2015;11(8):478–488. doi:10.1038/nrendo.2015.69
  • Loch Batista R, Inácio M, Prado Arnhold IJ, et al. Psychosexual aspects, effects of prenatal androgen exposure, and gender change in 46,XY disorders of sex development. J Clin Endocrinol Metab. 2019;104(4):1160–1170. doi:10.1210/jc.2018-01866
  • Berenbaum SA, Beltz AM. How early hormones shape gender development. Curr Opin Behav Sci. 2016;7:53–60. doi:10.1016/j.cobeha.2015.11.011
  • Berenbaum SA, Beltz AM. Sexual differentiation of human behavior: effects of prenatal and pubertal organizational hormones. Front Neuroendocrinol. 2011;32(2):183–200. doi:10.1016/j.yfrne.2011.03.001
  • Banerjee PP, Banerjee S, Brown TR, Zirkin BR. Androgen action in prostate function and disease. Am J Clin Exp Urol. 2018;6(2):62–77.
  • Imperato-McGinley J. 5alpha-reductase-2 deficiency and complete androgen insensitivity: lessons from nature. Adv Exp Med Biol. 2002;511:121–131; discussion 131–124.
  • Azzouni F, Godoy A, Li Y, Mohler J. The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol. 2012;2012:530121. doi:10.1155/2012/530121
  • Russell DW, Wilson JD. Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem. 1994;63:25–61. doi:10.1146/annurev.bi.63.070194.000325
  • Andersson S, Russell DW. Structural and biochemical properties of cloned and expressed human and rat steroid 5 alpha-reductases. Proc Natl Acad Sci U S A. 1990;87(10):3640–3644. doi:10.1073/pnas.87.10.3640
  • Wilson JD, Griffin JE, Russell DW. Steroid 5 alpha-reductase 2 deficiency. Endocr Rev. 1993;14(5):577–593. doi:10.1210/edrv-14-5-577
  • Wilson JD, Lasnitzki I. Dihydrotestosterone formation in fetal tissues of the rabbit and rat. Endocrinology. 1971;89(3):659–668. doi:10.1210/endo-89-3-659
  • Deykin JD, Balko C, Wilson JD. Recent studies on the mechanism of action of testosterone. N Engl J Med. 1972;287(25):1284–1291. doi:10.1056/NEJM197212212872508
  • Andersson S, Berman DM, Jenkins EP, Russell DW. Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature. 1991;354(6349):159–161. doi:10.1038/354159a0
  • Mendonca BB, Batista RL, Domenice S, et al. Steroid 5α-reductase 2 deficiency. J Steroid Biochem Mol Biol. 2016;163:206–211. doi:10.1016/j.jsbmb.2016.05.020
  • Costa EM, Domenice S, Sircili MH, Inacio M, Mendonca BB. DSD due to 5α-reductase 2 deficiency - from diagnosis to long term outcome. Semin Reprod Med. 2012;30(5):427–431. doi:10.1055/s-00000072
  • Livingstone DE, Di Rollo EM, Mak TC, Sooy K, Walker BR, Andrew R. Metabolic dysfunction in female mice with disruption of 5α-reductase 1. J Endocrinol. 2017;232(1):29–36. doi:10.1530/JOE-16-0125
  • Upreti R, Hughes KA, Livingstone DE, et al. 5α-reductase type 1 modulates insulin sensitivity in men. J Clin Endocrinol Metab. 2014;99(8):E1397–E1406. doi:10.1210/jc.2014-1395
  • Stiles AR, Russell DW. SRD5A3: a surprising role in glycosylation. Cell. 2010;142(2):196–198. doi:10.1016/j.cell.2010.07.003
  • Taylor RL, Arno G, Poulter JA, et al. Association of steroid 5α-reductase type 3 congenital disorder of glycosylation with early-onset retinal dystrophy. JAMA Ophthalmol. 2017;135(4):339–347. doi:10.1001/jamaophthalmol.2017.0046
  • Kara B, Ayhan Ö, Gökçay G, Başboğaoğlu N, Tolun A. Adult phenotype and further phenotypic variability in SRD5A3-CDG. BMC Med Genet. 2014;15:10. doi:10.1186/1471-2350-15-10
  • Cheng J, Lin R, Zhang W, et al. Phenotype and molecular characteristics in 45 Chinese children with 5α-reductase type 2 deficiency from South China. Clin Endocrinol (Oxf). 2015;83(4):518–526. doi:10.1111/cen.12799
  • Abacı A, Çatlı G, Kırbıyık Ö, et al. Genotype-phenotype 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:10.1007/s40618-018-0940-y
  • Gui B, Song Y, Su Z, et al. New insights into 5α-reductase type 2 deficiency based on a multi-centre study: regional distribution and genotype–phenotype profiling of SRD5A2 in 190 Chinese patients. J Med Genet. 2019;56:685–692. doi:10.1136/jmedgenet-2018-105915
  • Cohen-Kettenis PT. Gender change in 46,XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav. 2005;34(4):399–410. doi:10.1007/s10508-005-4339-4
  • Mendonca BB, Gomes NL, Costa EM, et al. 46,XY disorder of sex development (DSD) due to 17β-hydroxysteroid dehydrogenase type 3 deficiency. J Steroid Biochem Mol Biol. 2017;165(Pt A):79–85. doi:10.1016/j.jsbmb.2016.05.002
  • Inacio M, Sircili MH, Brito VN, et al. 46,XY DSD due to 17β-HSD3 deficiency and 5α-reductase type 2 deficiency. Adv Exp Med Biol. 2011;707:9–14.
  • Cools M, Nordenström A, Robeva R, et al. Caring for individuals with a difference of sex development (DSD): a Consensus Statement. Nat Rev Endocrinol. 2018;14(7):415–429. doi:10.1038/s41574-018-0010-8
  • Hiort O, Birnbaum W, Marshall L, et al. Management of disorders of sex development. Nat Rev Endocrinol. 2014;10(9):520–529. doi:10.1038/nrendo.2014.108
  • Wisniewski AB, Batista RL, Costa EMF, et al. Management of 46,XY differences/disorders of sex development (DSD) Throughout Life. Endocr Rev. 2019;40:1547–1572. doi:10.1210/er.2019-00049
  • Russell DW, Wilson JD. Chapter 4A - steroid 5α-reductase 2 deficiency. In: Minlptywomd H, editor. Genetic Steroid Disorders. San Diego: Academic Press; 2014:199–214.
  • Alswailem MM, Alzahrani OS, Alghofaili L, et al. Molecular genetics and phenotype/genotype correlation of 5-α reductase deficiency in a highly consanguineous population. Endocrine. 2019;63(2):361–368. doi:10.1007/s12020-018-1767-1
  • Avendaño A, Paradisi I, Cammarata-Scalisi F, Callea M. 5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review. Hormones (Athens). 2018;17(2):197–204. doi:10.1007/s42000-018-0013-9
  • 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):41–48. doi:10.1159/000271915
  • Yuan S, Meng L, Zhang Y, et al. Genotype-phenotype correlation and identification of two novel SRD5A2 mutations in 33 Chinese patients with hypospadias. Steroids. 2017;125:61–66. doi:10.1016/j.steroids.2017.06.010
  • Sahu R, Boddula R, Sharma P, et al. Genetic analysis of the SRD5A2 gene in Indian patients with 5alpha-reductase deficiency. J Pediatr Endocrinol Metab. 2009;22(3):247–254. doi:10.1515/JPEM.2009.22.3.247
  • Vilchis F, Méndez JP, Canto P, Lieberman E, Chávez B. Identification of missense mutations in the SRD5A2 gene from patients with steroid 5alpha-reductase 2 deficiency. Clin Endocrinol (Oxf). 2000;52(3):383–387. doi:10.1046/j.1365-2265.2000.00941.x
  • Samtani R, Bajpai M, Ghosh PK, Saraswathy KN. SRD5A2 gene mutations–a population-based review. Pediatr Endocrinol Rev. 2010;8(1):34–40.
  • Cheng T, Wang H, Han B, et al. Identification of three novel. Asian J Androl. 2019.
  • Bertelloni S, Baldinotti F, Russo G, et al. 5α-Reductase-2 deficiency: clinical Findings, endocrine pitfalls, and genetic features in a large Italian Cohort. Sex Dev. 2016;10(1):28–36. doi:10.1159/000445090
  • Berra M, Williams EL, Muroni B, et al. Recognition of 5α-reductase-2 deficiency in an adult female 46XY DSD clinic. Eur J Endocrinol. 2011;164(6):1019–1025. doi:10.1530/EJE-10-0930
  • Shabir I, Khurana ML, Marumudi E, Khadgawat R, Ammini AC. Novel nucleotide insertions in two unrelated Indian patients with 5 alpha reductase 2 deficiency leading to premature termination of SRD5A2 enzyme. Steroids. 2013;78(12–13):1159–1163 (Article). doi:10.1016/j.steroids.2013.08.010
  • Di Marco C, Bulotta AL, Varetti C, et al. Ambiguous external genitalia due to defect of 5-α-reductase in seven Iraqi patients: prevalence of a novel mutation. Gene. 2013;526(2):490–493. doi:10.1016/j.gene.2013.04.070
  • Hackel C, Oliveira LE, Ferraz LF, et al. New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2. J Mol Med (Berl). 2005;83(7):569–576. doi:10.1007/s00109-005-0651-7
  • Makridakis NM, Di Salle E, Reichardt JK. Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II. Pharmacogenetics. 2000;10(5):407–413. doi:10.1097/00008571-200007000-00004
  • Vilchis F, Valdez E, Ramos L, García R, Gómez R, Chávez B. Novel compound heterozygous mutations in the SRD5A2 gene from 46,XY infants with ambiguous external genitalia. J Hum Genet. 2008;53(5):401–406. doi:10.1007/s10038-008-0274-2
  • Zhu H, Liu W, Han B, et al. Phenotypic and molecular characteristics in eleven Chinese patients with 5α-reductase Type 2 deficiency. Clin Endocrinol (Oxf). 2014;81(5):711–720. doi:10.1111/cen.2014.81.issue-5
  • Katharopoulos E, Sauter K, Pandey AV, Flück CE. In silico and functional studies reveal novel loss-of-function variants of SRD5A2, but no variants explaining excess 5α-reductase activity. J Steroid Biochem Mol Biol. 2019;190:263–272. doi:10.1016/j.jsbmb.2019.01.017
  • Wigley WC, Prihoda JS, Mowszowicz I, et al. Natural mutagenesis study of the human steroid 5 alpha-reductase 2 isozyme. Biochemistry. 1994;33(5):1265–1270. doi:10.1021/bi00171a029
  • de la Chaux N, Messer PW, Arndt PF. DNA indels in coding regions reveal selective constraints on protein evolution in the human lineage. BMC Evol Biol. 2007;7:191. doi:10.1186/1471-2148-7-191
  • Lalonde S, Stone OA, Lessard S, et al. Frameshift indels introduced by genome editing can lead to in-frame exon skipping. PLoS One. 2017;12(6):e0178700. doi:10.1371/journal.pone.0178700
  • Wang GS, Cooper TA. Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet. 2007;8(10):749–761. doi:10.1038/nrg2164
  • Anna A, Monika G. Splicing mutations in human genetic disorders: examples, detection, and confirmation. J Appl Genet. 2018;59:253–268. doi:10.1007/s13353-018-0444-7
  • Hunt RC, Simhadri VL, Iandoli M, Sauna ZE, Kimchi-Sarfaty C. Exposing synonymous mutations. Trends Genet. 2014;30(7):308–321. doi:10.1016/j.tig.2014.04.006
  • Chávez B, Valdez E, Vilchis F. Uniparental disomy in steroid 5alpha-reductase 2 deficiency. J Clin Endocrinol Metab. 2000;85(9):3147–3150. doi:10.1210/jcem.85.9.6786
  • Deeb A, Al Suwaidi H, Ibukunoluwa F, Attia S. Phenotype, sex of rearing, gender re-assignment, and response to medical treatment in extended family members with a novel mutation in the SRD5A2 gene. J Clin Res Pediatr Endocrinol. 2016;8(2):236–240. doi:10.4274/jcrpe.2782
  • Fénichel P, Paris F, Philibert P, et al. Molecular diagnosis of 5α-reductase deficiency in 4 elite young female athletes through hormonal screening for hyperandrogenism. J Clin Endocrinol Metab. 2013;98(6):E1055–E1059. doi:10.1210/jc.2012-3893
  • Stankiewicz P, Lupski JR. Structural variation in the human genome and its role in disease. Annu Rev Med. 2010;61:437–455. doi:10.1146/annurev-med-100708-204735
  • Zhang F, Gu W, Hurles ME, Lupski JR. Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet. 2009;10:451–481. doi:10.1146/annurev.genom.9.081307.164217
  • Lisch D, Burns KH. Editorial overview: genome architecture and expression: mobile elements at work. Curr Opin Genet Dev. 2018;49:iv–v. doi:10.1016/j.gde.2018.05.003
  • Kazazian HH, Moran JV. Mobile DNA in health and disease. N Engl J Med. 2017;377(4):361–370. doi:10.1056/NEJMra1510092
  • Szafranski P, Kośmider E, Liu Q, et al. LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV. Hum Mutat. 2018;39(12):1916–1925. doi:10.1002/humu.23608
  • Batista RL, Yamaguchi K, Di Santi Rodrigues A, et al. Mobile DNA in endocrinology: LINE-1 retrotransposon causing partial androgen insensitivity syndrome. J Clin Endocrinol Metab. 2019;104:6385–6390. doi:10.1210/jc.2019-00144
  • Hancks DC, Kazazian HH. Roles for retrotransposon insertions in human disease. Mob DNA. 2016;7:9.
  • Ule J. Alu elements: at the crossroads between disease and evolution. Biochem Soc Trans. 2013;41(6):1532–1535. doi:10.1042/BST20130157
  • Batista RL, Di Santi Rodrigues A, Nishi MY, et al. A recurrent synonymous mutation in the human androgen receptor gene causing complete androgen insensitivity syndrome. J Steroid Biochem Mol Biol. 2017;174:14–16. doi:10.1016/j.jsbmb.2017.07.020
  • Batista RL, Rodrigues AS, Machado AZ, et al. Partial androgen insensitivity syndrome due to somatic mosaicism of the androgen receptor. J Pediatr Endocrinol Metab. 2018;31(2):223–228. doi:10.1515/jpem-2017-0095
  • Hornig NC, Ukat M, Schweikert HU, et al. Identification of an AR mutation-negative class of androgen insensitivity by determining endogenous AR activity. J Clin Endocrinol Metab. 2016;101(11):4468–4477. doi:10.1210/jc.2016-1990
  • Hornig NC, de Beaufort C, Denzer F, et al. A recurrent germline mutation in the 5ʹUTR of the androgen receptor causes complete androgen insensitivity by activating aberrant uORF translation. PLoS One. 2016;11(4):e0154158. doi:10.1371/journal.pone.0154158
  • Tirabassi G, Cignarelli A, Perrini S, et al. Influence of CAG repeat polymorphism on the targets of testosterone action. Int J Endocrinol. 2015;2015:298107. doi:10.1155/2015/298107
  • Chen R, Davydov EV, Sirota M, Butte AJ. Non-synonymous and synonymous coding SNPs show similar likelihood and effect size of human disease association. PLoS One. 2010;5(10):e13574. doi:10.1371/journal.pone.0013574
  • Hochberg Z, Chayen R, Reiss N, et al. Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5 alpha-reductase 2 deficiency. J Clin Endocrinol Metab. 1996;81(8):2821–2827. doi:10.1210/jcem.81.8.8768837
  • Palmer BW, Reiner W, Kropp BP. Proximal hypospadias repair outcomes in patients with a specific disorder of sexual development diagnosis. Adv Urol. 2012;2012:708301. doi:10.1155/2012/708301
  • Sun L, Zhou M, Liu T. Association between SRD5A2 polymorphism and hypospadias: a meta-analysis. Pharmazie. 2019;74(2):125–128. doi:10.1691/ph.2019.8768
  • Francis A, Sarkar S, Pooja S, et al. SRD5A2 gene polymorphisms affect the risk of breast cancer. Breast. 2014;23(2):137–141. doi:10.1016/j.breast.2013.11.010
  • Li Q, Zhu Y, He J, et al. Steroid 5-alpha-reductase type 2 (SRD5A2) V89L and A49T polymorphisms and sporadic prostate cancer risk: a meta-analysis. Mol Biol Rep. 2013;40(5):3597–3608. doi:10.1007/s11033-012-2434-x
  • Li J, Coates RJ, Gwinn M, Khoury MJ. Steroid 5-{alpha}-reductase Type 2 (SRD5a2) gene polymorphisms and risk of prostate cancer: a HuGE review. Am J Epidemiol. 2010;171(1):1–13. doi:10.1093/aje/kwp318
  • Silver RI, Russell DW. 5alpha-reductase type 2 mutations are present in some boys with isolated hypospadias. J Urol. 1999;162(3 Pt 2):1142–1145. doi:10.1016/S0022-5347(01)68102-3
  • Samtani R, Bajpai M, Ghosh PK, Saraswathy KN. A49T, R227Q and TA repeat polymorphism of steroid 5 alpha-reductase type II gene and hypospadias risk in North Indian children. Meta Gene. 2015;3:1–7. doi:10.1016/j.mgene.2014.11.003
  • Spurdle AB, Hopper JL, Chen X, et al. The steroid 5alpha-reductase type II TA repeat polymorphism is not associated with risk of breast or ovarian cancer in Australian women. Cancer Epidemiol Biomarkers Prev. 2001;10(12):1287–1293.
  • El Ezzi AA, Boyko VG, Baker MT, et al. Association of some polymorphisms in the VDR gene, CYP17 gene and SRD5A2 gene and prostate cancer among lebanese men. Asian Pac J Cancer Prev. 2017;18(1):93–100. doi:10.22034/APJCP.2017.18.1.93
  • Adiyaman PB, Ocal G, Cetinkaya E, et al. 5 alpha steroid reductase deficiency in Turkey. Pediatr Endocrinol Rev. 2006;3(Suppl 3):462–469.
  • Ocal G, Adiyaman P, Berberoğlu M, et al. Mutations of the 5alpha-steroid reductase type 2 gene in six Turkish patients from unrelated families and a large pedigree of an isolated Turkish village. J Pediatr Endocrinol Metab. 2002;15(4):411–421. doi:10.1515/JPEM.2002.15.4.411
  • Walter KN, Kienzle FB, Frankenschmidt A, 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:10.1159/000313372
  • 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):254–256. doi:10.5144/0256-4947.2014.254
  • Mazen I, Gad YZ, Hafez M, Sultan C, Lumbroso S. Molecular analysis of 5alpha-reductase type 2 gene in eight unrelated egyptian children with suspected 5alpha-reductase deficiency: prevalence of the G34R mutation. Clin Endocrinol (Oxf). 2003;58(5):627–631. doi:10.1046/j.1365-2265.2003.01763.x
  • Baldinotti F, Majore S, Fogli A, et al. Molecular characterization of 6 unrelated Italian patients with 5alpha-reductase type 2 deficiency. J Androl. 2008;29(1):20–28. doi:10.2164/jandrol.107.002592
  • Callens N, Van Kuyk M, van Kuppenveld JH, et al. Recalled and current gender role behavior, gender identity and sexual orientation in adults with disorders/differences of sex development. Horm Behav. 2016;86:8–20. doi:10.1016/j.yhbeh.2016.08.008
  • Kreukels BPC, Köhler B, Nordenström A, et al. Gender dysphoria and gender change in disorders of sex development/intersex conditions: results from the dsd-LIFE study. J Sex Med. 2018;15(5):777–785. doi:10.1016/j.jsxm.2018.02.021
  • Hines M. Gender development and the human brain. Annu Rev Neurosci. 2011;34:69–88. doi:10.1146/annurev-neuro-061010-113654
  • Hiort O. The differential role of androgens in early human sex development. BMC Med. 2013;11:152. doi:10.1186/1741-7015-11-152
  • Arnold AP. The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues. Horm Behav. 2009;55(5):570–578. doi:10.1016/j.yhbeh.2009.03.011
  • Bakula DM, Mullins AJ, Sharkey CM, Wolfe-Christensen C, Mullins LL, Wisniewski AB. Gender identity outcomes in children with disorders/differences of sex development: predictive factors. Semin Perinatol. 2017;41:214–217. doi:10.1053/j.semperi.2017.03.010
  • Zhang M, Yang J, Zhang H, Ning G, Li X, Sun S. A novel SRD5A2 mutation with loss of function identified in Chinese patients with hypospadias. Horm Res Paediatr. 2011;76(1):44–49.
  • Nagaraja MR, Rastogi A, Raman R, Gupta DK, Singh SK. Molecular diagnosis of 46,XY DSD and identification of a novel 8 nucleotide deletion in exon 1 of the SRD5A2 gene. J Pediatr Endocrinol Metab. 2010;23(4):379–385.