Non-Classical Congenital Adrenal Hyperplasia-Causing Alleles in Adolescent Girls with PCOS and in Risk Group for PCOS Development

Abstract

Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. Depending on the diagnostic criteria applied, it occurs in up to 16.6% of the general female population. Congenital adrenal hyperplasia includes a group of autosomal recessive disorders, the most common of which is non-classical congenital adrenal hyperplasia (NCAH) caused by mutations in the CYP21A2 gene. PCOS and NCAH have similar clinical manifestations (hyperandrogenemia, i.e., hirsutism, acne, alopecia, and increased androgen levels in the blood) and potential impact on long-term health (infertility, increased risk of type 2 diabetes, and cardiovascular disease. Consequently, it is thought that NCAH mutations in the heterozygous state may play a role in PCOS development and phenotypic expression. Objective: To determine the prevalence of the most common pathogenic alleles of the CYP21A2 gene in adolescents with PCOS and adolescents at risk of PCOS development, and to compare the results with healthy adolescents matched for gynecological age. Methods: A cross-sectional study was conducted with 55 PCOS patients, 23 risk patients (with hyperandrogenism but a normal menstrual cycle), and 49 healthy adolescents. Genetic variations in the CYP21A2 gene were analyzed using a standard Multiplex Ligation-dependent Probe Amplification test (SALSA MLPA Probemix P050-C1 CAH; MRC Holland). Results: No significant differences were found among the three groups regarding the frequency of carriers of NCAH variations in the heterozygous state. It was found that the I172N carrier in the PCOS group had a significantly higher Global Acne Grading Scale score than PCOS patients without this variation (p = 0.038). Within the control group of healthy adolescents, compound heterozygous carriers (IVS2-12A > G and -113G > A) had a significantly higher body mass index than non-carriers (p = 0.036). Conclusion: We found no differences in the incidence of NCAH-causing variations in the heterozygous state in adolescent PCOS patients, risk adolescents (with hirsutism but normal menstruation), and healthy adolescents. Future studies of larger cohorts and rarer pathogenic CYP21A2 gene variations are required.

A multidisciplinary approach in the management of patients with acne

“…Отримано свідчення, що мутація гена CYP17-34C (кодує цитохром P450c17a, який є одним із ключових ферментів синтезу андрогенів) призводить до виникнення акне тяжкого ступеня [26,15]. При мутаціях у гені CYP21A2 спостерігається вроджена гіперплазія кори надниркових залоз з порушенням синтезу андрогенів та варіабельністю клінічних проявів [46].…”

“…Дані, отримані у ході досліджень L. Lidaka et al та V. Caputo et al, свідчать про те, що у пацієнтів з мутаціями у гені 21-гідроксилази може спостерігатися синдром полікістозних яєчників (СПКЯ) та вугрова хво-роба, яка резистентна до стандартної терапії [46,25]. Разом із тим є повідомлення про те, що поширеність гетерозиготної мутації у гені CYP21A2 у пацієнтів з акне вище, ніж серед здорової популяції [36].…”

Survey based on classification of PCOS using gene expression

“…Figure 2 shows the general architecture to diagnose PCOS using gene expression. [2][3][4][5][6][7][8][9][10]. using above mention techniques we can identified the PCOS gene.…”

Characterization of Mutations Causing CYP21A2 Deficiency in Brazilian and Portuguese Populations

“…However, 17OHP can be altered by a deficiency in other enzymes in the steroidogenic pathway, in premature infants, and in unrelated diseases causing physiologic stress [ 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 ]. Therefore, the molecular diagnosis is essential for the confirmation of complex cases and follow-up management of asymptomatic CAH, avoiding unnecessary treatment, along with genetic counseling [ 11 , 16 , 17 ].…”

“…The biochemical correlation for CYP21A2 activity works well for the CAH diagnosis. However, external factors or a combination of genetic diseases can change the steroid levels, making genotype elucidation an important tool for patient management [ 11 , 17 ]. In general, there is a good genotype-phenotype correlation for CAH, and the elucidation of new variants found in each population is important to improve the correct treatment [ 25 , 26 ].…”