What genetic basis is primarily associated with Congenital Adrenal Hyperplasia?

Congenital Adrenal Hyperplasia (CAH) is predominantly caused by mutations in the CYP21A2 gene, which encodes the enzyme steroid 21-hydroxylase. This enzyme is crucial in the adrenal gland's steroidogenic pathway, as it catalyzes the conversion of progesterone to 11-deoxycorticosterone and 17-hydroxyprogesterone to 11-deoxycortisol. A deficiency in this enzyme leads to an accumulation of steroid precursors and a decrease in the production of cortisol and aldosterone, which can result in various hormonal imbalances and clinical manifestations, including adrenal crisis, ambiguous genitalia in females, and precocious puberty in males.

The other genes mentioned are associated with different conditions. The AR gene is linked to androgen insensitivity syndrome, CHD7 is associated with CHARGE syndrome, and WT1 is related to Wilms' tumor and disorders affecting the development of gonads and kidneys. None of these genes play a direct role in the pathophysiology of CAH, making CYP21A2 the primary gene associated with this condition.