POPULATION-WIDE EVALUATION OF DISEASE MANIFESTATION IN RELATION TO MOLECULAR GENOTYPE IN STEROID 21-HYDROXYLASE (CYP21) DEFICIENCY - GOOD CORRELATION IN A WELL-DEFINED POPULATION

We report a population-wide analysis of all patients with 21-hydroxyla se deficiency (21-OHD) found in Finland, a country with a genetically well defined population, in which the effects of other genetic and env ironmental factors on the phenotype can be expected to be low. In tota l, 120 patients were identified, and their clinical status was evaluat ed. Blood samples for CYP21 genotype determination could be obtained f rom 78 (65%) patients, and their phenotypes were compared with their g enotypes. In general, the severity of gene defects correlated well wit h clinical expression. All patients carrying mutations with the most d rastic effects on enzymatic activity had the salt-wasting form of 21-O HD. The I2 splice mutation, which in some reports has been connected w ith clinical variation, was constantly associated with severe mineralo corticoid deficiency. However, patients with I172N as the determining mutation expressed a wide spectrum of phenotypes; the variation could not be attributed to additional mutations. Although genetically affect ed males with the nonclassical form had not been clinically diagnosed, our study suggests that nonclassical 21-OHD is substantially more rar e in Finland than elsewhere, as indicated by both clinical evaluation and mutational screening.