title: Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients.
abstract: BACKGROUND
  In 46,XY disorders of sex development, 5α-reductase deficiency is rare and is not usually the first-intention diagnosis in newborn ambiguous genitalia, contrary to partial androgen insensitivity syndrome. Yet the cause of ambiguous genitalia may guide sex assignment, and rapid, precise diagnosis of 5α-reductase deficiency is essential.
  
  
  OBJECTIVE
  The aim of the study was to describe relevant data for clinical diagnosis, biological investigation, and molecular determination from 55 patients with srd5A2 mutations identified in our laboratory over 20 yr to improve early diagnosis.
  
  
  METHODS
  The study was performed at Montpellier University Hospital.
  
  
  METHODS
  We studied a cohort of 55 patients with srd5A2 gene mutations.
  
  
  METHODS
  Genetic analysis of srd5A2 was conducted.
  
  
  RESULTS
  Clitoromegaly (49.1%) and microphallus with various degrees of hypospadias (32.7%) were frequent phenotypes. Female external genitalia (7.3%) and isolated micropenis (3.6%) were rare. Seventy-two percent of patients were initially assigned to female gender; five of them (12.5%) switched to male sex in peripuberty. Over 72% of patients were considered for 5α-reductase deficiency diagnosis when the testosterone/dihydrotestosterone cutoff was 10. In 55 patients (with 20 having a history of consanguinity), we identified 33 different mutations. Five have never been reported: p.G32S, p.Y91H, p.G104E, p.F223S, and c.461delT. Homozygous mutations were present in 69.1% of cases, compound heterozygous mutations in 25.5%, and compound heterozygous mutations alone with the V89L polymorphism in 5.4%. Exons 1 and 4 were most affected, with 35.8 and 21.7% mutant alleles per exon, respectively.
  
  
  CONCLUSIONS
  In the largest cohort to date, we demonstrate a wide spectrum of phenotypes and biological profiles in patients with 5α-reductase deficiency, whatever their geographical or ethnic origins.
authors.affiliation: Service d'Hormonologie, Hôpital Lapeyronie, Centre Hospitalier Universitaire (CHU) Montpellier and Université Montpellier I, 34295 Montpellier, France.
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authors.forename: Horia
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authors.forename: Cristóbal J del Valle
authors.initials: CJ
authors.lastname: Nuñez
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mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D000293:Adolescent; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D013734:Androgen-Insensitivity Syndrome / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D013196:Dihydrotestosterone / Q000097:blood; D012734:Disorders of Sex Development / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005836:Genitalia, Female / Q000002:abnormalities; D005837:Genitalia, Male / Q000002:abnormalities; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D013196:Dihydrotestosterone; D013739:Testosterone; D004247:DNA; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human