A Novel 13-bp Deletion in Exon 1 of CYP21 Gene Causing Severe Congenital Adrenal Hyperplasia

Abstract

Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase gene (CYP21). In most cases, this defect is the result of gene conversion events between the functional CYP21 gene and the adjacent inactive pseudogene (CYP21P). Previous screening for mutations of 21-hydroxylase gene in 51 unrelated Tunisian CAH patients revealed 4 novel mutations that have not been reported to occur in the CYP21P pseudogene. The present paper describes the fifth new small 13-bp deletion in exon 1 found after sequencing the CYP21 gene of a Tunisian patient suffering from the salt-wasting form of CAH. The patient is a girl born to consanguineous parents; she is homozygous for a novel deletion. The 13-bp deletion causes a stop codon at amino acid 47, which is likely to result in an enzyme with no activity. Both parents are heterozygous for the small deletion as confirmed by nested PCR method. This novel mutation has not been reported to occur in the CYP21P pseudogene, indicating a casual mutagenic event rather than a conversion one.