ESPE Abstracts (2015) 84 P-2-314

Pubertal Virilization in Two Unrelated XY Teenagers with Female Phenotype due to NR5A1/SF-1 Gene Mutation

Pascal Philiberta,e, Patrick Fenichelb, Didier Dewaillyc, Françoise Audrand, Nadege Fauconnet-Servantd, Françoise Parisa & Charles Sultana

aCHRU and Université de Montpellier, Montpellier, France; bCHU and Université de Nice-Sophia Antipolis, Nice, France; cCHRU and Université de Lille, Lille, France; dCHRU de Montpellier, Montpellier, France; eInstitut de Génétique Humaine – CNRS UPR1142, Montpellier, France

Background: Pubertal virilization in a 46,XY DSD patient is generally due to partial androgen insensitivity, 5-alpha-reductase deficiency, or 17-ketoreductase deficiency. Recently, reports have identified virilization signs associated with NR5A1/SF-1 gene mutations.

Cases presentation and method: We present two unrelated cases of pubertal virilization due to NR5A1/SF-1 gene mutation. Both were suspected to be primarily affected by 5-alpha-reductase deficiency but no mutation was identified within the SRD5A2 gene coding sequence. The first case was a young high-level female athlete with biological and clinical signs of hypervirilization. The second case was a girl first investigated in infancy for coalescence of the labia minora. At this time, the karyotype revealed a discordant 46,XY formula. Genetic investigation of the SRD5A2 gene identified no abnormality. When she was 15 years old, her physician observed striking signs of virilization: clitoromegaly, high plasma testosterone (8.2 ng/ml) and high FSH (45 UI/l) contrasting with normal LH (6 UI/l).

Results: Genetic investigation of the first case revealed a de novo deletion, c.361delG, in exon 4 that led to a frameshift and premature stop codon. In the second case, we identified an 11-nucleotide deletion (c.630_640delGTACGGCTACC) in exon 4 that led to a frameshift and premature stop codon.

Conclusions: We report two new NR5A1/SF-1 deletions in 46,XY DSD girls with pubertal virilization. In both cases, the initial diagnosis was 5-alpha-reductase deficiency. In addition to 5-alpha-reductase and 17-ketoreductase deficiencies, these data suggest that NR5A1/SF-1 should systematically be investigated in XY adolescent girls with virilization at puberty.

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