Combined 17 Alpha - Hydroxylase / 17 , 20 - Lyase Defi ciency due to a Homozygous 25 BP Duplication ( NT 4157 - 4181 ) at Exon 5 in the CYP 17 Resulting in a Premature Stop Codon Predicted

Combined 17alpha-hydroxylase/17,20-lyase defi ciency is a rare, autosomal recessive form of congenital adrenal hyperplasia characterized by the coexistence of hypertension, caused by the hyperproduction of mineralocorticoid precursors and DSD in males and sexual infantilism in females, due to impaired production of sex hormones. Several CYP17 mutations resulting in 17alpha-hydroxylase/17,20-lyase defi ciency have been reported previously. In the present study, we described a novel CYP17 mutation in two Brazilian sisters with primary amenorrhea, 46,XY karyotype, high basal levels of progesterone (3.4-4.9 ng/mL) and hypokalemic hypertension born to consanguineous parents. After PCR and automatic sequencing of CYP17 coding region, 25 bp duplication at exon 5 was found in the patients. This duplication started at codon 318 resulting in a premature stop codon at position 320 resulting in an ineffective and truncated protein and in accordance with the molecular modeling of P450c17. Therefore we expanded the repertoire of CYP17 mutations describing the largest duplication found in this gene in both sisters, with a clinical phenotype of combined 17alpha-hydroxylase/17,20-lyase defi ciency and emphasizes the importance of the P450c 17 molecular modeling to predict the functional effect of these mutations. (Arq Bras Endocrinol Metab 2008; 52/8:1317-1320)