Abstract
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.
2009 Massachusetts Medical Society
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Androgens / blood
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Androstenedione / blood
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Child
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Dehydroepiandrosterone / blood
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Dehydroepiandrosterone / metabolism
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Diagnosis, Differential
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Female
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Heterozygote
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Humans
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Multienzyme Complexes / deficiency
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Multienzyme Complexes / genetics*
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Multienzyme Complexes / metabolism
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Mutation*
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Polycystic Ovary Syndrome / diagnosis
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Puberty, Precocious / blood
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Puberty, Precocious / genetics*
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RNA, Messenger / metabolism
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Sequence Analysis, DNA
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Sulfate Adenylyltransferase / deficiency
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Sulfate Adenylyltransferase / genetics*
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Sulfate Adenylyltransferase / metabolism
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Sulfotransferases / blood
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Sulfotransferases / metabolism
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Testosterone / blood
Substances
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Androgens
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Multienzyme Complexes
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RNA, Messenger
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Testosterone
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Androstenedione
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Dehydroepiandrosterone
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PAPS synthetase
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Sulfate Adenylyltransferase
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Sulfotransferases
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dehydroepiandrosterone sulfotransferase