TY - JOUR
T1 - Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency
T2 - An extensive international experience of 55 patients
AU - Maimoun, Laurent
AU - Philibert, Pascal
AU - Cammas, Benoit
AU - Audran, Françoise
AU - Bouchard, Philippe
AU - Fenichel, Patrick
AU - Cartigny, Maryse
AU - Pienkowski, Catherine
AU - Polak, Michel
AU - Skordis, Nicos
AU - Mazen, Inas
AU - Ocal, Gonul
AU - Berberoglu, Merih
AU - Reynaud, Rachel
AU - Baumann, Clarisse
AU - Cabrol, Sylvie
AU - Simon, Dominique
AU - Kayemba-Kay's, Kabangu
AU - De Kerdanet, Marc
AU - Kurtz, François
AU - Leheup, Bruno
AU - Heinrichs, Claudine
AU - Tenoutasse, Sylvie
AU - Van Vliet, Guy
AU - Grüters, Annette
AU - Eunice, Marumudi
AU - Ammini, Ariachery C.
AU - Hafez, Mona
AU - Hochberg, Ze'ev
AU - Einaudi, Sylvia
AU - Al Mawlawi, Horia
AU - Del Valle Nuñez, Cristóbal J.
AU - Servant, Nadège
AU - Lumbroso, Serge
AU - Paris, Françoise
AU - Sultan, Charles
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79951711611&partnerID=8YFLogxK
U2 - 10.1210/jc.2010-1024
DO - 10.1210/jc.2010-1024
M3 - Article
C2 - 21147889
AN - SCOPUS:79951711611
SN - 0021-972X
VL - 96
SP - 296
EP - 307
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -