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. 2011 Feb;96(2):296-307.
doi: 10.1210/jc.2010-1024. Epub 2010 Dec 8.

Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients

Laurent Maimoun  1 , Pascal Philibert, Benoit Cammas, Françoise Audran, Philippe Bouchard, Patrick Fenichel, Maryse Cartigny, Catherine Pienkowski, Michel Polak, Nicos Skordis, Inas Mazen, Gonul Ocal, Merih Berberoglu, Rachel Reynaud, Clarisse Baumann, Sylvie Cabrol, Dominique Simon, Kabangu Kayemba-Kay's, Marc De Kerdanet, François Kurtz, Bruno Leheup, Claudine Heinrichs, Sylvie Tenoutasse, Guy Van Vliet, Annette Grüters, Marumudi Eunice, Ariachery C Ammini, Mona Hafez, Ze'ev Hochberg, Sylvia Einaudi, Horia Al Mawlawi, Cristóbal J del Valle Nuñez, Nadège Servant, Serge Lumbroso, Françoise Paris, Charles Sultan
Affiliations

Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients

Laurent Maimoun et al. J Clin Endocrinol Metab. 2011 Feb.

Abstract

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.

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