[Gene heterogeneity in adrenal 21-hydroxylase]

Abstract

Congenital adrenal hyperplasia caused by 21-hydroxylase deficiency is a recessive autosomal genetic disease due to lesion of the gene coding for cytochrome P450c21. Classically, congenital adrenal hyperplasia is divided into two types: one virilizing and called congenital, with or without loss of salt, the other called late onset. In reality, behind this oversimplification lies a clinically, biochemically and genetically heterogeneous disease. Clinical and laboratory findings reflect a continuous impairment of 21-hydroxylase activity. A study of the CYP21B gene located in an important duplicated region of the genome (short arm of chromosome 6, between the HLA-B and -DR loci) where numerous rearrangements take place confirm this heterogeneity. About 25 percent of CYP21B gene lesions are deletions or conversions of a long fragment of the CYP21B gene into the CYP21A pseudogene. The other lesions (75 percent) consist of point mutations that are all present in the CYP21A pseudogene, which suggests microconversion between the two genes. Determining these lesions in the patients provide a better understanding of the clinical heterogeneity and will soon be the basis of the prenatal diagnosis.