Variations in the 3'UTR of the Gene in Heterozygous Females with Hyperandrogenaemia.

Heterozygosity for mutations in females is possibly related to increased risk of developing clinical hyperandrogenism. The present study was designed to seek evidence on the phenotype-genotype correlation in female children, adolescents, and women with mutations and variants in the 3'UTR region of the gene. Sixty-six patients out of the 169 were identified as carriers of mutations. Higher values of stimulated 17 hydroxyprogesterone (17-OHP) levels were found in the carriers of the p.Val281Leu mutation compared to the carriers of other mutations (mean: 24.7 nmol/l versus 15.6 nmol/l). The haplotype of the 52C>T, 440C>T, and 443T>C in the 3'UTR was identical in all heterozygous patients with p.Val281Leu and the haplotype of the 12C>T and 52C>T was identical in all heterozygous patients with the p.Gln318. In conclusion, hyperandrogenaemic females are likely to bear heterozygous mutations. Carriers of the mild p.Val281Leu mutation are at higher risk of developing hyperandrogenism than the carriers of more severe mutations. The identification of variants in the 3'UTR of in combination with the heterozygous mutation may be associated with the mild form of nonclassic congenital adrenal hyperplasia and reveal the importance of analyzing the untranslated regions for the appropriate management of this category of patients.