The disease is caused by biallelic mutations in the CYP17A1 gene, encoding the enzyme 17[alpha]-hydroxyprogesterone (OHP) aldolase (Cytochrome P450c17) catalyzing the conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione ([DELTA]4A) via 17[alpha]-hydroxylation and the 17,20-lyase reaction.
Mutation of proline 409 to arginine in the meander region of cytochrome p450c17 causes severe 17 alpha-hydroxylase deficiency.
The present report describes a CAH patient with 46,XY disorder of sex development due to cytochrome P450c17 deficiency caused by the homozygous g.4869T>A; g.4871delC (p.Y329Kfs?) mutation in exon 6 of CYP17A1 gene.
Although further research occurs, this work sheds new light on role of cytochrome P450c17 in the steroidogenesis at both the adrenal and the gonadal level and on the harmful consequences of its deficiency in the short and long term, respectively.
Auchus, "Fertility in patients with genetic deficiencies of cytochrome P450c17 (CYP17A1): combined 17-hydroxylase/17,20-lyase deficiency and isolated 17,20-lyase deficiency," Fertility and Sterility, vol.
Waterman, "Biochemical differences between rat and human cytochrome P450c17
support the different steroidogenic needs of these two species," Biochemistry, vol.
Some studies have focused on the ultrastructure and morphology of the different cell types present in each layer of the adrenal cortex and medulla during intrauterine development and the immunolocalization of steroidogenic enzymes, especially that responsible for androgens production, as cytochrome P450c17 in species of wild mammals (Quinn et al., 2013).
The aims of present study were compare the morphometric data between left and right adrenal of males and females; perform a histological, scanning and transmission electron microscopy study showing tissue constitution of glands; finally, in order to define the presence and correct site of the cytochrome P450c17 expression in adrenal glands, immunohistochemical study of this enzyme was performed.
17OHD has an autosomal recessive heritage and cytochrome P450c17 enzyme gene locus is 10q24-q25.
Cytochrome P450c17 (steroid 17a-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues.
has two enzyme activities, 17-alpha-hydroxylase and 17,20-lyase.
Mutation R96W in cytochrome P450c17
gene causes combined 17 alpha-hydroxylase/17-20-lyase deficiency in two French Canadian patients.