MUTATIONAL SPECTRUM OF THE STEROID 21-HYDROXYLASE GENE IN SWEDEN - IMPLICATIONS FOR GENETIC DIAGNOSIS AND ASSOCIATION WITH DISEASE MANIFESTATION

We have characterized the disease-causing mutations in the steroid 21- hydroxylase genes of 127 patients with different clinical forms of con genital adrenal hyperplasia, representing 186 unrelated chromosomes. T he gene was completely absent on 29.8% of the chromosomes, and this to gether with the I2 splice (27.7%), I173N (20.8%), V282L (5.4%), and R3 57W (3.8%) mutations constitute 87.5% of all affected chromosomes. In total, 15 different sequence aberrations combine to form 19 different disease-causing alleles. The results confirm that genotyping is an eff icient means of diagnosing steroid 21-hydroxylase deficiency, although special consideration is needed to resolve genotypes when full famili es are not available. Clinical presentations of the different combinat ions of mutations indicate that genotyping is reliable for prediction of clinical outcome in patients with 21-hydroxylase deficiency. It is especially helpful in determining whether in, utero treatment of affec ted females is indicated and in classifying the severity of 81-hydroxy lase deficiency in children diagnosed through neonatal screening, befo re symptoms have appeared.