BACKGROUND

Steroid 11β-hydroxylase deficiency (11OHD) is the second most common cause of congenital adrenal hyperplasia. Inherited in an autosomal recessive manner, 11OHD is caused by mutations in the CYP11B1 gene.

OBJECTIVE

To identify the mutation causing 11OHD in a Chinese pedigree and analyze the functional consequences and phenotype associated with this mutation.

METHODS

A Chinese family with 11OHD was screened for mutations in the CYP11B1 gene. Mini-gene experiment was performed to mimic the natural splicing and outcome of the genetic variation.

RESULTS

Complete DNA sequencing of the CYP11B1 gene revealed a novel 449-bp homozygous deletion (g.2697del449) in the patient and a heterozygous deletion in both of the patient's parents and sister. This mutation was predicted to lead to the skipping of part of exon 3 and all of exon 4 and inserting of part of intron 4 in the CYP11B1 mRNA. It generated a truncated protein and resulted in the complete destruction of the heme-binding domain of the enzyme.

CONCLUSIONS

The novel deletion drastically affects normal protein structure and abolishes normal enzyme activity, leading to a severe phenotype of congenital adrenal hyperplasia due to 11OHD.