AN UPDATE ON THE MOLECULAR-GENETICS OF CONGENITAL ADRENAL-HYPERPLASIA- DIAGNOSTIC AND THERAPEUTIC ASPECTS

An update on the molecular genetics of congenital adrenal hyperplasia due to 21-hydroxylase deficiency is given. In Sweden, direct mutation detection has been used for genetic diagnosis of this disease since 19 90. Around 400 affected 21-hydroxylase genes have been analyzed so far . Mutations that have arisen by interaction with the adjacent pseudoge ne, including gene deletion and nine smaller sequence aberrations, are responsible for the disease in around 95% of alleles. A total of 13 r are, mostly population-specific mutations have been characterized amon g the remaining 5%, Some of these rare mutations are present in the ps eudogene at a low frequency, indicating that they have started to spre ad at a low rate in the population. The mutations can be divided into different groups according to severity, This makes it possible to pred ict clinical outcome in affected subjects based on genotyping. The ris k of salt-wasting and prenatal virilization can be estimated, and over treatment can be avoided in mildly affected cases.