通过从斯洛伐克和斯洛文尼亚的先天性肾上腺增生症（CAH）患者中分析突变谱、临床特征、基因型表型相关性、睾丸上贾氏瘤患病率和新生儿筛查的作用，获得了104例CAH患者的数据，这些数据来自斯洛伐克和斯洛文尼亚数据库。使用低分辨率基因分型法检测最常见的点突变。为了检测CYP21A2基因的缺失、转换、点突变或其他序列变化，使用高分辨率基因分型法。根据残留的21-羟化酶活性（null、A、B、C），将基因型分类。64%的个体属于失盐型（SW-CAH），15%的个体属于单纯男性化型（SV-CAH），21%的个体属于非经典型（NC-CAH）。CYP21A2基因缺失/转换和c.293-13A/C>G致病变异共占受影响等位基因的55.5%。在SV-CAH中，p.Ile172Asn是最常见的致病变异（28.13%），而在NC-CAH中是p.Val282Leu（33.33%）、CYP21A2基因缺失/转换（21.43%）、c.293-13A/C>G（14.29%）和Pro30Leu（11.90%）。在斯洛文尼亚患者中，多个致病变异的等位基因频率较高（占所有等位基因的15.83%）。严重基因型（0和A）与预期表型（SW中的94.74%和97.3%）相关良好，而较轻的基因型（B和C）相关较弱（SV中的50%和NC中的70.8%）。在斯洛伐克，SW-CAH患者在诊断时的中位数年龄是6天，而在斯洛文尼亚是28.5天（p=0.01）。在队列中的大多数斯洛伐克患者是通过新生儿筛查检测出来的（29人中的24人）。在24名男性患者中，发现了7例TARTs，全部（100%）都患有SW-CAH并且荷尔蒙控制不良。TARTs的诊断中位数年龄为13岁。本研究验证了新生儿筛查的重要性，特别是在诊断严重形式的CAH中的速度方面。在严重致病变异的情况下，预测21-OH缺陷表型是相当好的，但在较轻的致病变异的情况下则不太可靠，这与其他人群的数据相一致。对于所有CAH男性患者，应该实现TARTs筛查，因为早期识别时有可能发生缓解。版权所有©2023 Saho、Dolzan、Zerjav Tansek、Pastorakova、Petrovic、Knapkova、Trebusak Podkrajsek、Suput Omladic、Bertok、Avbelj Stefanija、Kotnik、Battelino、Pribilincova和Groselj。

To analyze the mutational spectrum, clinical characteristics, genotype-phenotype correlations, testicular adrenal rests tumor prevalence, and role of neonatal screening in congenital adrenal hyperplasia (CAH) patients from Slovakia and Slovenia.Data were obtained from 104 patients with CAH registered in Slovak and Slovenian databases. Low-resolution genotyping was performed to detect the most common point mutations. To detect deletions, conversions, point mutations, or other sequence changes in the CYP21A2 gene, high-resolution genotyping was performed. Genotypes were classified according to residual 21-hydroxylase activity (null, A, B, C).64% of the individuals had the salt-wasting form (SW-CAH), 15% the simple virilizing form (SV-CAH), and 21% the non-classic (NC-CAH). CYP21A2 gene deletion/conversion and c.293-13A/C>G pathogenic variant accounted together for 55.5% of the affected alleles. In SV-CAH p.Ile172Asn was the most common pathogenic variant (28.13%), while in NC-CAH p.Val282Leu (33.33%), CYP21A2 gene deletion/conversion (21.43%), c.293-13A/C>G (14.29%), Pro30Leu (11.90%). The frequency of alleles with multiple pathogenic variants was higher in Slovenian patients (15.83% of all alleles). Severe genotypes (0 and A) correlated well with the expected phenotype (SW in 94.74% and 97.3%), while less severe genotypes (B and C) correlated weaklier (SV in 50% and NC in 70.8%). The median age of SW-CAH patients at the time of diagnosis was 6 days in Slovakia vs. 28.5 days in Slovenia (p=0.01). Most of the Slovak patients in the cohort were detected by NBS. (24 out of 29). TARTs were identified in 7 out of 24 male patients, of whom all (100%) had SW-CAH and all had poor hormonal control. The median age at the diagnosis of TARTs was 13 years.The study confirmed the importance of neonatal screening, especially in the speed of diagnosis of severe forms of CAH. The prediction of the 21-OH deficiency phenotype was reasonably good in the case of severe pathogenic variants, but less reliable in the case of milder pathogenic variants, which is consistent compared to data from other populations. Screening for TARTs should be realized in all male patients with CAH, since there is possible remission when identified early.Copyright © 2023 Saho, Dolzan, Zerjav Tansek, Pastorakova, Petrovic, Knapkova, Trebusak Podkrajsek, Suput Omladic, Bertok, Avbelj Stefanija, Kotnik, Battelino, Pribilincova and Groselj.