Two intronic variants of CYP11B1 and CYP17A1 disrupt mRNA splicing and cause congenital adrenal hyperplasia (CAH).

Objectives: Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder of steroidogenesis.11β-hydroxylase deficiency and 17α-hydroxylase deficiency are two forms of CAH caused by defects of CYP11B1 and CYP17A1 respectively. Case presentation: Two rare intronic variants were identified in suspected CAH patients. Though not located at the classic splicing sites, these two variants perturbed splicing based on minigene assays. One variant, NM_000497.4: c.240-157T>G of CYP11B1 identified in subject 1, resulted in the retention of 136 intronic nucleotides. The other variant, NM_000102.4: c.754-6 A>G of CYP17A1 identified in subject 2, leading to the retention of 5 intronic nucleotides. Both variants resulted in out-of-frame alteration of the respective transcript. Conclusion: Cryptic splicing variants in the intronic regions contribute to the genetic defects of CAH. Minigene assay is useful to confirm the splice altering effect and make a definitive molecular diagnosis. [ABSTRACT FROM AUTHOR]