Abstract | BACKGROUND: SUBJECTS AND METHODS: Clinical assessment, endocrine evaluation, and genetic analysis were performed in one female and one male with 46,XY DSD who showed spontaneous virilization during puberty. The female patient presented at adolescence with clitoral hypertrophy, whereas the male patient presented at birth with severe hypospadias and entered puberty spontaneously. Molecular analysis of NR5A1 was performed followed by in vitro functional analysis of the two novel mutations detected. RESULTS:
Testosterone levels were normal during puberty in both patients. Analysis of NR5A1 revealed two novel heterozygous missense mutations in the ligand-binding domain of SF-1 (patient 1: p.L376F; patient 2: p.G328V). The mutant proteins showed reduced transactivation of the CYP11A promoter in vitro. CONCLUSION: Patients with 46,XY DSD and NR5A1 mutations can produce sufficient testosterone for spontaneous virilization during puberty. Phenotypic females (46,XY) with NR5A1 mutations can present with clitoromegaly at puberty, a phenotype similar to other partial defects of androgen synthesis or action. Testosterone production in 46,XY males with NR5A1 mutations can be sufficient for virilization at puberty. As progressive gonadal dysgenesis is likely, gonadal function should be monitored in adolescence and adulthood, and early sperm cryopreservation considered in male patients if possible.
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Authors | Sally Tantawy, Lin Lin, Ilker Akkurt, Guntram Borck, Dietrich Klingmüller, Berthold P Hauffa, Heiko Krude, Heike Biebermann, John C Achermann, Birgit Köhler |
Journal | European journal of endocrinology
(Eur J Endocrinol)
Vol. 167
Issue 1
Pg. 125-30
(Jul 2012)
ISSN: 1479-683X [Electronic] England |
PMID | 22474171
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- NR5A1 protein, human
- Steroidogenic Factor 1
- Testosterone
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Topics |
- Adolescent
- Adult
- Disorder of Sex Development, 46,XY
(blood, genetics)
- Female
- Humans
- Male
- Mutation
- Puberty
(genetics)
- Steroidogenic Factor 1
(genetics)
- Testosterone
(blood, genetics)
- Virilism
(blood, genetics)
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