Non-classical congenital adrenal hyperplasia (NC-CAH) includes a group of genetic disorders due to a broad class of CYP21A2 variants identifying a disease-causing 'C' genotype. The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated. With the aim of obtaining a more accurate delineation of the phenotype of heterozygous carrier of CAH, we analyzed clinical, biochemical and molecular characteristics in a cohort of Sicilian subjects. Fifty-seven females with biallelic and monoallelic CYP21A2 variants classifying NC-CAH (24) and heterozygous carriers of CAH (33), respectively were selected. Forty-four females age-matched healthy controls were also enrolled and genotyped for CYP21A2. Clinical, hormonal and genetic data were collected. CYP21A2 monoallelic mutations, defining the heterozygous carriers state, were identified in subjects with clinical features including hirsutism, oligomenorrhoea, overweight and a PCO-like phenotype, particularly occurring in the age of adolescence. Consistently, levels of 17OHP and cortisol were found to be significantly different from NC-CAH. Overall, some clinical and laboratory findings including oligomenorrhea and 17OHP/cortisol ratio were observed as independent markers associated with carriers of CAH. Here we report a high prevalence of late-onset signs of polycystic ovary syndrome (PCOS) and hyperandrogenism in heterozygous carriers. The 17OHP/cortisol ratio may be a predictive tool to identify the carriers of CAH, even though specific cut-off values have not yet been identified.

中文翻译：

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先天性肾上腺增生杂合子携带者的临床和激素特征。

非经典的先天性肾上腺皮质增生（NC-CAH）包括一组遗传疾病，这是由于广泛的CYP21A2变体类型识别出引起疾病的“ C”基因型所致。CYP21突变的杂合子携带者发生临床上明显的雄激素过多的风险增加，即使临床和实验室特征仍被低估。为了更准确地描述CAH杂合子载体的表型，我们分析了西西里受试者的临床，生化和分子特征。选择57名具有双等位基因和单等位基因CYP21A2变体的女性，分别对NC-CAH（24）和CAH的杂合子进行分类（33）。还招募了44名年龄匹配的女性健康对照者，并对其进行了CYP21A2基因分型。临床，收集激素和遗传数据。CYP21A2单等位基因突变定义了杂合子携带者的状态，已确定具有临床特征的受试者，包括多毛症，少月经，超重和PCO样表型，尤其是在青春期。一致地，发现17OHP和皮质醇的水平与NC-CAH显着不同。总体而言，观察到一些临床和实验室检查结果，包括少经和17OHP /皮质醇比值是与CAH携带者相关的独立标志物。在这里，我们报道了杂合子携带者中多囊卵巢综合征（PCOS）和雄激素过多症的晚期发病迹象的高患病率。即使尚未确定特定的临界值，17OHP /皮质醇比也可能是识别CAH携带者的预测工具。