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Population-Wide Evaluation of Disease Manifestation in Relation to Molecular Genotype in Steroid 21-Hydroxylase (CYP21) Deficiency: Good Correlation in a Well Defined Population¹

Department of Pediatrics, Kuopio University Hospital (J.J., R.V.), FIN-70211 Kuopio; and the Finnish Red Cross Blood Transfusion Service, Tissue Typing Laboratory (A.L., J.P.), FIN-00310 Helsinki, Finland

Address all correspondence and requests for reprints to: Dr. J. Jääskeläinen, Department of Pediatrics, Kuopio University Hospital (J.J., R.V.), P.O. Box 1777, FIN-70211 Kuopio, Finland.

We report a population-wide analysis of all patients with 21-hydroxylase deficiency (21-OHD) found in Finland, a country with a genetically well defined population, in which the effects of other genetic and environmental factors on the phenotype can be expected to be low. In total, 120 patients were identified, and their clinical status was evaluated. Blood samples for CYP21 genotype determination could be obtained from 78 (65%) patients, and their phenotypes were compared with their genotypes. In general, the severity of gene defects correlated well with clinical expression. All patients carrying mutations with the most drastic effects on enzymatic activity had the salt-wasting form of 21-OHD. The I2 splice mutation, which in some reports has been connected with clinical variation, was constantly associated with severe mineralocorticoid 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 affected males with the nonclassical form had not been clinically diagnosed, our study suggests that nonclassical 21-OHD is substantially more rare in Finland than elsewhere, as indicated by both clinical evaluation and mutational screening.

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