Combined 17alpha-
hydroxylase/
17,20-lyase deficiency 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 deficiency 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 deficiency and emphasizes the importance of the P450c 17 molecular modeling to predict the functional effect of these mutations.