Background

Congenital adrenal hyperplasia (CAH) due to autosomal recessive 21-hydroxylase deficiency (21-OHD) is caused by defects in the CYP21 (CYP21A2) gene. Several mutations have been identified in the CYP21 (CYP21A2) gene of patients with 21-OHD. We aimed at determining the frequency of these mutations among a group of Egyptian patients and studying the genotype–phenotype correlation.

Methods

Forty-seven patients with CAH due to 21-OHD from 42 different families diagnosed by clinical and hormonal evaluation and classified accordingly into salt wasting (SW) and simple virilizing (SV) phenotypes were enrolled. Their ages ranged between 1.78 and 18.99 years. Molecular analysis of the CYP21 (CYP21A2) gene was performed for the detection of eleven common mutations: P30L, I2 splice (I2 G), Del 8 bp E3 (G110del8nt), I172N, cluster E6 (I236N, V237E, M239K), V281L, L307 frameshift (F306 + T), Q318X, R356W, P453S, R483P by polymerase chain reaction (PCR) and reverse hybridization.

Results

Disease-causing mutations were identified in 47 patients, 55.31% of them were compound heterozygous. The most frequent mutations were I2 splice (25.43%), followed by cluster E6 (16.66%) and P30L (15.78%). Two point mutations (P453S, R483P) were not identified in any patient. In the SW patients, genotypes were more compatible with their phenotypes.

Conclusion

Molecular characterization should be considered along with clinical and biochemical diagnosis of CAH since it could confirm the diagnosis, outline the treatment strategy and morbidity, and ensure proper genetic counseling.

中文翻译：

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内婚人群中 21-羟化酶缺乏的基因型谱

背景

常染色体隐性遗传 21-羟化酶缺乏 (21-OHD) 引起的先天性肾上腺增生 (CAH) 是由 CYP21 (CYP21A2) 基因缺陷引起的。已经在 21-OHD 患者的 CYP21 (CYP21A2) 基因中发现了几个突变。我们旨在确定一组埃及患者中这些突变的频率，并研究基因型-表型相关性。

方法

招募了来自 42 个不同家庭的 47 名 CAH 患者，这些患者来自 42 个不同的家庭，通过临床和激素评估诊断并相应地分为盐消耗 (SW) 和简单男性化 (SV) 表型。他们的年龄介于 1.78 和 18.99 岁之间。对 CYP21 (CYP21A2) 基因进行分子分析以检测 11 种常见突变：P30L、I2 剪接 (I2 G)、Del 8 bp E3 (G110del8nt)、I172N、簇 E6 (I236N、V237E、M239K)、V281L、 L307 移码 (F306 + T)、Q318X、R356W、P453S、R483P 通过聚合酶链式反应 (PCR) 和反向杂交。

结果

47例患者发现致病突变，其中55.31%为复合杂合子。最常见的突变是 I2 剪接 (25.43%)，其次是簇 E6 (16.66%) 和 P30L (15.78%)。在任何患者中均未发现两个点突变（P453S、R483P）。在 SW 患者中，基因型与其表型更相容。

结论

分子特征应与 CAH 的临床和生化诊断一起考虑，因为它可以确认诊断，概述治疗策略和发病率，并确保适当的遗传咨询。