Subject:
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IGMD 6: Hormonal regulation IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism ONCOL 3: Translational research ONCOL 5: Aetiology, screening and detection |
Organization:
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Paediatrics Laboratory of Genetic, Endocrine and Metabolic Diseases |
Journal title:
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The New England Journal of Medicine
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Abstract:
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Dehydroepiandrosterone (DHEA) sulfotransferase, known as SULT2A1, converts the androgen precursor DHEA to its inactive sulfate ester, DHEAS [corrected], thereby preventing the conversion of DHEA to an active androgen. SULT2A1 requires 3'-phosphoadenosine-5'-phosphosulfate (PAPS) for catalytic activity. We have identified compound heterozygous mutations in the gene encoding human PAPS synthase 2 (PAPSS2) in a girl with premature pubarche, hyperandrogenic anovulation, very low DHEAS levels, and increased androgen levels. In vitro coincubation of human SULT2A1 and wild-type or mutant PAPSS2 proteins confirmed the inactivating nature of the mutations. These observations indicate that PAPSS2 deficiency is a monogenic adrenocortical cause of androgen excess.
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