TRUE PRECOCIOUS PUBERTY AND HETEROZYGOSITY FOR THE STEROID 21-HYDROXYLASE DEFICIENCY. MOLECULAR STUDY

Abstract

In order to detect heterozygous carriers of the gene for congenital adrenal hyperplasia (21 hydroxylase deficiency; CAH), 32 girls affected by true precocious puberty were studied by the single-dose ACTH stimulation test and by HLA typing. Moreover, molecular analysis of CYP21B gene with PCR technique using specific oligonucleotides for the mutated site, was performed in 7 cases. After ACTH testing, 13 of 32 (41%) cases displayed an increment of 17-OHP and/or 21 deoxycortisol greater than normal and similar to that observed in obligate hetorozigotes. On correlating the HLA phenotype with the ACTH response, we found that the 13 cases assumed to be heterozygotes on the basis of ACTH test, had an increased frequency of the A28 (38.5% vs 7.3%) and B14 (53.8% vs 7.1%) antigens and the remaining 19 patients with normal response to ACTH had an increased frequency of B22 (21.1% vs 3.4%). Molecular analysis showed that 4 of 7 haplotypes carrying the HLA B14 allele, were characterized by the mutation Val 281-Leu. This mutation results in an enzyme with 50% of normal activity when 17-OHP is the substrate, but only 20% of normal activity for progesterone.