title: Primary amenorrhea in four adolescents revealed 5α-reductase deficiency confirmed by molecular analysis.
abstract: OBJECTIVE
  To determine the genetic cause of primary amenorrhea.
  
  
  METHODS
  Case series.
  
  
  METHODS
  Pediatric endocrinology, endocrinology, and gynecology departments of academic hospitals.
  
  
  METHODS
  Three adolescents and one young woman 46, XY patients with srd5A2 gene mutations.
  
  
  METHODS
  Genetic analysis of srd5A2.
  
  
  RESULTS
  We report four srd5A2 gene mutations in three adolescents and one young woman with 46,XY primary amenorrhea. All presented clitoromegaly and two presented hypospadias; all had been reared as females. Virilization of the external genitalia was noted in the pubertal period in all four patients. Three were maintained in the female sex of rearing by personal choice, and the fourth switched gender. We identified the homozygous substitutions p.L55Q (exon 1), p.Q56R (exon 1), and p.N193S (exon 4), in patients 1, 2, and 3, respectively. Patient 4 had compound heterozygous mutations, a new c.34delG (exon 1) associated with p.R246W (exon 5). All patients had high plasma T levels (ranges, 16.2-23.2 nmol/L; normal female teenage range, 0.35-2 nmol/L).
  
  
  CONCLUSIONS
  Our data clearly demonstrate that 5α-reductase deficiency should be considered in XY adolescents with primary amenorrhea and no breast development associated with virilization at puberty and high plasma T. Positive parental consanguinity should reinforce the diagnostic orientation.
authors.affiliation: Service d'Hormonologie, Hôpital Lapeyronie, CHU Montpellier, and UMI Montpellier, Montpellier, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Maimoun
authors.forename: Pascal
authors.initials: P
authors.lastname: Philibert
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouchard
authors.forename: Gönül
authors.initials: G
authors.lastname: Ocal
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.forename: Patrick
authors.initials: P
authors.lastname: Fenichel
authors.forename: Nadège
authors.initials: N
authors.lastname: Servant
authors.forename: Françoise
authors.initials: F
authors.lastname: Paris
authors.forename: Charles
authors.initials: C
authors.lastname: Sultan
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D000568:Amenorrhea / Q000175:diagnosis* / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D025202:Molecular Diagnostic Techniques; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human