Nonclassic 11β-hydroxylase deficiency with hypofunctional polymorphisms on both haplotype
Sang-Yong Kim, Hak-Yeon Bae & Jin-Hwa Kim
11β-hydroxylase deficiency (11β-OHD), an autosomal recessive disorder, is the second most common cause of congenital adrenal hyperplasia. It is caused by the mutation of the CYP11B1 gene that encodes the enzyme. In classical 11β-OHD, genetic mutations of CYP11B1 lead to activity decrease or loss, but mutations in nonclassical 11β-OHD are not definite. The vast majority of mutations are associated with classic 11β-OHD, and only a few mutations causing nonclassic 11β-OHD have been described as yet. We report analysis of the CYP11B1 genes of adult man thought to suffer from nonclassic 11β-OHD.
A 24-year-old man presented with hypokalemia and borderline hypertension. Hormonal studies and physical finding established diagnosis of nonclassic 11β-OHD; elevated plasma levels of ACTH, 11-deoxycortisol, 17-hydroxyprogesteron, androstenedione, low levels of cortisol. ACTH stimulated serum cortisol levels were low. Basal and ACTH stimulated serum 11-deoxycortisol levels were 138 and 739 ng/ml, respectively (normal, 0120 ng/ml). Basal and ACTH stimulated serum 17-hydroxyprogesteron levels were 47.6 and 272 ng/ml, respectively (normal, 0.63.42 ng/ml). Abdomen computed tomography revealed both adrenal gland hyperplasia. To determine the molecular genetic defects, genomic DNA was isolated from the leukocytes. The coding and intronexon junction regions of CYP11B1 were totally sequenced. We find two hypofunctional genetic polymorphisms of CYP11B1 gene that were c.128G>A and c.595+12G>A. Each polymorphism were located on different haplotype. These findings suggest that this hypofunctional polymorphisms on both haplotype affects 11β-hydroxylase function, resulting in the clinical features of nonclassic 11β-OHD.