<unk> -hydroxylase CAH is inherited in an autosomal recessive fashion The CYP<unk> A2 gene for the P450c21 enzyme (also known as<unk> -hydroxylase) is at 6p21.3, amid genes HLA B and HLA DR coding for the major human histocompatibility loci (HLA). CYP21A2 is paired with a nonfunctional pseudogene CYP21A1P. Scores of abnormal alleles of CYP21A2 have been documented, most arising from recombinations of homologous regions of CYP21A2 and CYP21A1P. The<unk> -hydroxylase<unk>  may be caused by macrodeletions of about 30 Kb, which includes not only most of the 5′ region of the CYP21A2 gene, but also all of the C4B gene and 3′ regions of the CYP21A1P pseudogene. Duplications of CYP21A1P pseudogene and C4B gene are often associated with nonclassic<unk> -hydroxylase<unk> .<unk>  to the high degree of homology between the CYP21A2 gene and the CYP21A1P pseudogene, and the complexity of the locus, research on the molecular level is difficult. Differences in residual enzyme activity of the various alleles account for the various degrees of severity of the disease. Inheritance of all forms of<unk> -hydroxylase CAH is autosomal recessive. Persons affected by any forms of the disease have two abnormal alleles, and both parents are usually heterozygotes (or carriers). When both parents carry an abnormal allele, each child has a 25% chance of having the disease, a 50% chance of being a carrier like the parents, and a 25% chance of having two normal genes. It is now possible to test for heterozygosity by measuring 17α-hydroxyprogesterone elevation after ACTH stimulation, or more recently by direct gene sequencing. More than 200 disease-causing variants within the CYP21A2 gene have been identified so far that lead to<unk> -hydroxylase<unk>  if at least two of these variants are present as compound heterozygous. There is a good correlation between the genotype and phenotype. As a result, the CYP21A2 genotyping has high diagnostic value. However, the genotyping of the CYP21A2 gene is prone to errors, especially<unk>  to the closely located and highly homologous pseudogene CYP21A1P and the complex duplications, deletions and rearrangements within the chromosome 6p21.3. That's why CYP21A2 genotyping, interpretation of the results, and adequate genetic counseling for patients and their families requires deep understanding of CYP21A2 genetics.
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency
Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency
Primary pigmented nodular adrenocortical disease
Lipoid congenital adrenal hyperplasia
Cortisone reductase deficiency
Pituitary ACTH hypersecretion