An intron 1 splice mutation and a nonsense mutation (W23X) in CYP21 causing severe congenital adrenal hyperplasia.

Direct DNA sequencing of the steroid 21-hydroxylase gene (CYP21) revealed two novel mutations in two patients with severe congenital adrenal hyperplasia. The nonsense mutation Trp23Stop (TGG --> TGA) was found in a woman with the simple virilizing form of the disease. She was a compound heterozygote, with the previously described Ile173Asn mutation on her other allele. A boy, who developed salt-wasting in the neonatal period, carried an allele with a novel mutation of the canonical splice acceptor site in intron 1 (AG --> GG). He was also a compound heterozygote, with the well-known splice mutation in intron 2 on his other allele.