CONTEXT: 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.
SETTING: The study was performed at Montpellier University Hospital.
PATIENTS: We studied a cohort of 55 patients with srd5A2 gene mutations.
MAIN OUTCOME MEASURE(S): 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.