Screening for mutations of 21-hydroxylase gene in hungarian patients with congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diso rders, causing impaired secretion of cortisol and aldosterone from the adre nal cortex, with subsequent overproduction of adrenal androgens. The most c ommon enzyme defect causing CAH is steroid 21-hydroxylase deficiency. To de termine the mutational spectrum in the Hungarian CAH population, the CYP21 active gene was analyzed using PCR. A total of 297 Hungarian patients with 21-hydroxylase deficiency are registered in the 2nd Department of Pediatric s, Budapest, Hungary, and their clinical status was evaluated. Blood sample s for CYP21 genotype determination could be obtained from 167 patients (rep resenting 306 unrelated chromosomes and 56.2% of the total group of patient s). Eight of the most common mutations were screened [In2 (intron 2 splice mutation), I172N, Del (Del: apparents large gene conversion), Q318X, R356W, 1761Tins, ClusterE6, V281L] using allele-specific amplification. The most frequent mutation in the Hungarian CAH population was found to be In2. Our results have shown a good genotype/phenotype correlation in case of most mu tations; the In2 mutation is associated mostly with the severe form of the disease, whereas I172N was expressed in a wide spectrum of phenotypes.