Missense mutation serine106----proline causes 17 alpha-hydroxylase deficiency.

Article Details

Citation

Lin D, Harikrishna JA, Moore CC, Jones KL, Miller WL

Missense mutation serine106----proline causes 17 alpha-hydroxylase deficiency.

J Biol Chem. 1991 Aug 25;266(24):15992-8.

PubMed ID
1714904 [ View in PubMed
]
Abstract

Steroid 17 alpha-hydroxylase deficiency is caused by defects in cytochrome P450c17, the single enzyme that has 17-alpha hydroxylase and 17,20-lyase activities. We describe a rapid and efficient polymerase chain reaction tactic for identifying these genetic lesions and identify Ser106----Pro as the cause of 17 alpha-hydroxylase deficiency in two unrelated homozygous patients from Guam. We used site-directed mutagenesis of the normal P450c17 cDNA to construct the Pro106 mutant, and expressed both the normal and mutant sequences in monkey COS-1 cells and in yeast. Expression of the normal sequence permitted the cells to convert pregnenolone to 17-OH pregnenolone, progesterone to 17-OH progesterone, and 17-OH pregnenolone to dehydroepiandrosterone, showing the normal sequence conferred both 17 alpha-hydroxylase and 17,20-lyase activities. Expression of the mutant sequence generated P450c17 mRNA, but conferred none of these activities, proving that the Ser106----Pro mutation abolished the 17 alpha-hydroxylase and 17,20-lyase activities. An HhaI restriction site created by the mutation should permit screening of large populations.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Steroid 17-alpha-hydroxylase/17,20 lyaseP05093Details