Novel mutation in cytochrome P450c17 causes complete combined 17alpha-hydroxylase/17,20-lyase deficiency.

Abstract

BACKGROUND:

Cytochrome P450c17 (CYP17) has two principal enzyme activities, 17alpha-hydroxylase and 17,20-lyase, which are required for cortisol and androgen biosynthesis, respectively. Mutations in the gene encoding for CYP17 result in 17alpha-hydroxylase deficiency (17OHD), a rare form of congenital adrenal hyperplasia, a disorder characterized by adrenal insufficiency, hypertension, primary amenorrhea and sexual infantilism. We describe a case of complete combined 17OHD caused by mutations in the CYP17 gene.

PATIENT:

This study evaluates a 19 year-old Korean female born from a non-consanguineous relationship who presented with primary amenorrhea, hypertension, hyperpigmentation, absent axillary hair and pubic hair, and Tanner I breasts. Laboratory evaluation showed markedly elevated adrenocorticotropin and 11-deoxycorticosterone with suppressed plasma renin, aldosterone, and cortisol, consistent with 17OHD.

METHODS:

Genomic DNA was isolated from peripheral blood leukocytes. The eight exons of the human CYP17 gene were amplified in four segments by polymerase chain reaction. Amplicons were gel-purified and directly sequenced.

RESULTS:

The patient was found to be compound heterozygous for mutations in exon 6: a novel mutation R358X (CGA--TGA) and Y329 del/ sub (TAC-->AA). Both alterations introduce premature stop codons prior to the hemebinding cysteine and are predicted to completely inactivate the encoded P450c17 proteins.

CONCLUSION:

This patient is a compound heterozygote for nonsense mutations in the CYP17 gene, which confirms the diagnosis of 17OHD.

• Authors: Amrit Bhangoo, Javier Aisenberg, Amy Chartoffe, Svetlana Ten, Robert J Wallerstein, Robin Wolf, Richard J Auchus
• Journal: Journal of pediatric endocrinology & metabolism : JPEM (J Pediatr Endocrinol Metab) Vol. 21 Issue 2 Pg. 185-90 (Feb 2008) ISSN: 0334-018X [Print] Germany
• PMID: 18422032 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Nonsense
• DNA
• Steroid 17-alpha-Hydroxylase

Topics

• Adrenal Hyperplasia, Congenital (enzymology, genetics)
• Adult
• Codon, Nonsense (genetics)
• DNA (genetics)
• Female
• Heterozygote
• Humans
• Male
• Pedigree
• Polymerase Chain Reaction
• Steroid 17-alpha-Hydroxylase (genetics)