Differences in hormonal levels between heterozygous CYP21A2 pathogenic variant carriers, non-carriers, and females with non-classic congenital hyperplasia

AUTOR(ES)

Silva, Rita Santos; Carvalho, Berta; Pedro, Jorge; Castro-Correia, Cíntia; Carvalho, Davide; Carvalho, Filipa; Fontoura, Manuel

FONTE

Archives of Endocrinology and Metabolism

DATA DE PUBLICAÇÃO

2022

RESUMO

ABSTRACT Objective: CYP21A2 mutation heterozygote carriers seem to have an increased risk of hyperandrogenism. However, the clinical relevance of the heterozygote carrier status and the reliability of hormonal testing in discriminating a carrier from a non-carrier are puzzling questions. We aimed to characterize a population of Portuguese females suspected of having non-classic congenital adrenal hyperplasia (NC-CAH) due to clinical and biochemical criteria and who have undergone CYP21A2 molecular analysis. Subjects and methods: Retrospectively, we have analyzed the clinical records of 131 females (32 girls aged 3-9 and 99 adolescents and premenopausal women aged 13-49) who underwent complete CYP21A2 molecular analysis due to suspicion of NC-CAH. We divided included participants into three groups according to the CYP21A2 molecular analysis: NC-CAH females (46), heterozygous carriers (49), and wild type (36). We then compared clinical signs and symptoms as well as biochemical and molecular data between carriers and NC-CAH individuals and between carriers and wild type females. We measured 17OHP by electrochemiluminescence immunoassay. Results: Clinical features were similar between groups. Heterozygous carriers presented higher basal and post-cosyntropin 17-hydroxyprogesterone (17OHP) than wild type individuals (p < 0.05) and lower basal and stimulated 17OHP levels than NC-CAH patients (p < 0.05). We discovered a considerable overlap between 17OHP levels among groups. The most common pathogenic variant we identified was p.Val282Leu. Conclusion: In this population of hyperandrogenic women and children, heterozygous carriers showed higher basal and stimulated 17OHP than non-carriers although normal basal and stimulated 17OHP responses do not exclude heterozygosity for CYP21A2 pathogenic variants. In this study, only the molecular analysis presented good sensitivity in identifying heterozygotes.

Documentos Relacionados

• Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia
• New mutations in CYP21A2 and CYP11B1 genes and their effects upon the enzimatic activities
• Direct molecular diagnosis of CYP21 mutations in congenital adrenal hyperplasia.
• Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing
• Heterozigose para mutação no gene CYP21A2 considerada como deficiência de 21-hidroxilase na triagem neonatal