Genotype-Phenotype Correlation in CAH Patients with Severe CYP21A2 Point Mutations in the Republic of Macedonia
Genotype-Phenotype Correlation in CAH Patients with Severe CYP21A2 Point Mutations in the Republic of Macedonia
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DOI：
10.1515/jpem.2010.147
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发表时间：
2010-09-01
影响因子：
1.4
通讯作者：
Kocova, Mirjana
中科院分区：
文献类型：
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作者：
Anastasovska, Violeta;Kocova, Mirjana
类固醇21-羟化酶缺乏是先天性肾上腺皮质增生（CAH）的最常见原因，由于CYP 21 A2基因突变。大约75%的患者与经典形式的CAH有严重损害的21-hydroxylase activity.Methods：我们进行了直接的分子诊断的9个常见的CYP 21 A2点突变在24马其顿CAH患者从20个无关的家庭，使用差异PCR和ACRS.Results：五个分析的突变被检测到23例：15例患者为一个突变的纯合子，4例患者为复合杂合子，4例患者为杂合子。IVS 2 - 13 A/C突变频率最高（60.4%），其次为Q318 X（22.9%）、R356 W（4.2%）、V281 L（2.1%）和P30 L（2.1%）。在患者的基因型表型的一致性是83.3%，完全一致的基因型预测SW和SV phenotype.Conclusion：在马其顿CAH患者中检测到的突变的分布与其他欧洲人群中所描述的相似。在我们的患者中观察到的基因型-表型相关性加强了基因型不能完全预测表型的事实。
Steroid 21-hydroxylase deficiency is a most frequent cause of congenital adrenal hyperplasia (CAH), due to mutations in the CYP21A2 gene. Approximately 75% of patients with classical form of CAH have severe impairment of 21-hydroxylase activity.Methods: We have performed direct molecular diagnosis of the nine common CYP21A2 point mutations in 24 Macedonian CAH patients from 20 unrelated families, using differential PCR and ACRS.Results: Five of the analysed mutations were detected in 23 patients: 15 patients were homozygous for one mutation, four patients were compound heterozygotes and four patients were heterozygotes. The most common was IVS2-13A/C mutation found in 60.4% of the alleles, followed by Q318X (22.9%), R356W (4.2%), V281L (2.1%) and P30L (2.1%). The concordance of genotype to phenotype in the patients was 83.3% with complete concordance in the genotypes predicting the SW and SV phenotype.Conclusion: The distribution of the detected mutations in the Macedonian CAH patients was similar with those described in other European populations. The genotype-phenotype correlation observed in our patients strengthens the fact that the genotype cannot be completely predictive of phenotype.