A novel compound heterozygous mutation of K494_V495 deletion plus R496L and D487_F489 deletion in extreme C-terminus of cytochrome P450c17 causes 17alpha-hydroxylase deficiency.

Abstract

17alpha-Hydroxylase deficiency is a rare disease caused by mutation of the CYP17 gene, resulting in hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism, low blood cortisol and low plasma renin activity. Herein, we report a female Taiwanese with 17alpha-hydroxylase deficiency. The CYP17 genes of this patient and five members of her family were analyzed by PCR-direct sequencing. One allele of the patient contains a 9-bp (c. 1459-1467 GACTCTTTC: D487, S488, F489) deletion, which is prevalent in Southeast Asia. The other allele has a 6-bp (c. 1480-1485 AAGGTG: K494, V495) deletion and an R496L (c. 1487 G>T) missense mutation, which is a novel mutation. Site-directed mutagenesis, in vitro expression and functional analysis in HEK-293T cells showed that this novel mutation [K494_V495 Del; R496L] resulted in complete loss of 17alpha-hydroxylase and 17,20-lyase activity. Thus this novel mutation in the extreme C-terminus abolishes enzyme activity, and when accompanied by a 9-bp deletion at codons 487-489 in the other allele, results in 17alpha-hydroxylase/17,20-lyase deficiency in this patient.

• Authors: Long-Shyong Lee, Wei-Jane Shu, Chen-Ming Wu, Chia-Hsing Hsieh, Su-Mei Chen, Chaur-Jong Hu, Wei-Yi Chen, Bon-Chu Chung
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 249 Issue 1-2 Pg. 16-20 (Apr 25 2006) ISSN: 0303-7207 [Print] Ireland
• PMID: 16483711 (Publication Type: Case Reports, Journal Article)

Chemical References

• Steroid 17-alpha-Hydroxylase

Topics

• Adrenal Hyperplasia, Congenital (genetics)
• Adult
• Alleles
• Cell Line
• DNA Mutational Analysis
• Female
• Humans
• Mutagenesis, Site-Directed
• Pedigree
• Rare Diseases (genetics)
• Sequence Deletion
• Steroid 17-alpha-Hydroxylase (genetics, metabolism)
• Taiwan (ethnology)