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Identification and Functional Characterization of a Large Deletion of the CYP11B1 Gene Causing an 11β-Hydroxylase Deficiency in a Chinese Pedigree

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.