21-Hydroxylase Deficiency molecular genetic studies

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Template:21-Hydroxylase Deficiency Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Molecular Genetic Studies

The CYP21 gene for the P450c21 enzyme (also known as 21-hydroxylase) is at 6p21.3, amid genes HLA B and HLA DR coding for the major human histocompatibility loci (HLA). CYP21 is paired with a nonfunctional pseudogene CYP21A. Scores of abnormal alleles of CYP21 have been documented, most arising from recombinations of homologous regions of CYP21 and CYP21A. Differences in residual enzyme activity of the various alleles account for the various degrees of severity of the disease. Inheritance of all forms of 21-hydroxylase CAH is autosomal recessive.

Persons affected by any forms of the disease have two abnormal alleles, and both parents are usually carriers (heterozygotes). When parents both carry an abnormal allele, each child has a 25% chance of having the disease, a 50% chance of being an asymptomatic carrier like parents, and a 25% chance of having two normal genes.

It is now possible to test for heterozygosity by measuring 17-hydroxyprogesterone elevation after ACTH stimulation, or more recently by direct gene sequencing.