%0 Journal Article
%T Nonclassic Congenital Adrenal Hyperplasia
%A Selma Witchel
%A Ricardo Azziz
%J International Journal of Pediatric Endocrinology
%D 2010
%I BioMed Central
%R 10.1155/2010/625105
%X Nonclassic congenital adrenal hyperplasia (NCAH) due to P450c21 (21-hydroxylase) deficiency is a common autosomal recessive disorder due to mutations in the CYP21A2 gene. This disorder was first described in 1957 by Decourt et al. [1]. Reported prevalences in women with androgen excess range from 0.6% to 9% (Table 1). Higher prevalences have been reported in Ashkenazi Jewish, Mediterranean, Middle-Eastern and Indian populations. Reported gene frequencies vary among ethnic groups and geographic region [2, 3].NCAH due to mutations in other steroidogenic enzyme genes, such as 11-hydroxylase (CYP11B1) and 3-hydroxysteroid dehydrogenase (HSD3B2), is extremely rare [4, 5]. The phenotypic spectrum for mutations in the cytochrome P450 oxidoreductase (POR) gene has been expanded to include amenorrhea, infertility, and low sex steroid hormone levels [6]. Partial loss of function missense mutations in the steroidogenic acute regulatory protein (StAR) gene has been associated with nonclassic lipoid adrenal hyperplasia; mutations in the ACTH receptor (MC2R) gene or the melanocortin 2 receptor accessory protein (MRAP) gene are associated with phenotypes similar to nonclassic lipoid adrenal hyperplasia [7]. This review will focus on NCAH due to CYP21A2 mutations.To date, 127 mutations have been reported in CYP21A2 (http://www.hgmd.cf.ac.uk/ webcite); these mutations range from complete loss of enzyme function to partial enzyme activity. Most of the mutations result from recombination between the active gene, CYP21A2, and its highly homologous non-functional pseudogene, CYP21A1P(i.e., gene conversion), which is located in close proximity within the HLA region on chromosome 6p21.3. Nevertheless, approximately 10¨C12 mutations account for the majority of the affected alleles. The majority of the CYP21A2 mutations reported to date are associated with simple virilizing or salt-wasting classic congenital adrenal hyperplasia (CAH). Functional studies indicate that these mutations result i
%U http://www.ijpeonline.com/content/2010/1/625105