More than 95% of congenital adrenal hyperplasia cases are due to mutations in CYP21A2, the gene encoding the adrenal steroid 21-hydroxylase enzyme (P450c21).
More than 95% of congenital adrenal hyperplasia (CAH) cases are associated with mutations in the 21-hydroxylase gene (CYP21A2) in the human leukocyte antigen (HLA) class III area on the short arm of chromosome 6p21.3.
The simple virilizing (SV) form of congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder usually caused by steroid 21-hydroxylase deficiency due to I172N missense mutation at the CYP21A2 gene.
Anticipation of the phenotypes associated with different combinations of CYP21A2 mutations remains the most important determinant in prenatal diagnosis and counseling of the expectant couple who are determined to be at risk for congenital adrenal hyperplasia.
Many patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency have CAH-X syndrome, a connective tissue dysplasia consistent with hypermobility-type Ehlers-Danlos syndrome due to a contiguous gene deletion involving the adjacent CYP21A2 and TNXB genes.
Establishing a diagnosis of congenital adrenal hyperplasia on the basis of biochemical and clinical data is occasionally challenging, and the identification of CYP21A2 mutations may help confirm the diagnosis.
Classical 21-hydroxylase deficiency (21-OHD) due to mutations in the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene is the most common type of congenital adrenal hyperplasia (CAH).
There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(rs7755898" genes_norm="1589">Q319*), formerly rs7755898" genes_norm="1589">Q318X, rs7755898) variant of the CYP21A2 gene.
Mutations of CYP21A2 variably decrease 21-hydroxylase activity and result in a spectrum of disease expressions in patients with congenital adrenal hyperplasia (CAH).
The CYP21A2 mutations that are in linkage disequilibrium with particular HLA-A, -B, -DRB1 alleles/haplotypes, cause deficiency of the 21-hydroxylase enzyme (21-OHD) and account for the majority of congenital adrenal hyperplasia (CAH) cases.
Steroid 21-hydroxylase deficiency (21-OHD) caused by the CYP21A2 gene mutations accounts for more than 90% of congenital adrenal hyperplasia (CAH) cases.
Some variants that cause autosomal-recessive congenital adrenal hyperplasia (CAH) also cause hypermobility type Ehlers-Danlos syndrome (EDS) due to the monoallelic presence of a chimera disrupting two flanking genes: CYP21A2, encoding 21-hydroxylase, necessary for cortisol and aldosterone biosynthesis, and TNXB, encoding tenascin-X, an extracellular matrix protein.