Clinical Phenotype and Mutation Spectrum of the CYP21A2 Gene in Patients with Steroid 21-Hydroxylase Deficiency
Clinical Phenotype and Mutation Spectrum of the CYP21A2 Gene in Patients with Steroid 21-Hydroxylase Deficiency
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DOI：
10.1055/s-0031-1287789
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发表时间：
2012-01-01
影响因子：
1.8
通讯作者：
Yoo, H. -W.
中科院分区：
文献类型：
--
作者：
Choi, J. -H.;Jin, H. -Y.;Yoo, H. -W.
类固醇21-羟化酶缺乏症是由CYP 21 A2基因失活突变引起的。本文报道了21-羟化酶缺乏症的突变谱及其基因型与表型的相关性。72例无血缘关系的先天性肾上腺皮质增生症（CAH）患者被纳入。通过多重连接依赖性探针扩增（MLPA）分析和使用4对序列特异性引物对CYP 21 A2和CYP 21 A1 P基因进行序列特异性差异PCR扩增，然后对整个CYP 21 A2基因进行测序，对CYP 21 A2进行分子分析。在144个不相关的CAH等位基因中，45个（31.3%）发现了大的基因缺失，而最常见的点突变是内含子2剪接突变（c.293- 13 A> G）（41/144，28.5%）。MLPA分析成功识别了72例CYP 21 A2单拷贝缺失患者中的23例（31.9%）。本文介绍了一种快速准确的21-羟化酶缺乏症的分子诊断方法，该方法依赖于CYP 21 A2基因内点突变和结构重排的鉴定。
Steroid 21-hydroxylase deficiency is caused by inactivating mutations in the CYP21A2 gene. This paper reports on the mutation spectrum and the genotype-phenotype correlation of 21-hydroxylase deficiency. 72 unrelated patients with congenital adrenal hyperplasia (CAH) were included. Molecular analysis of CYP21A2 was performed, via the multiplex ligation-dependent probe amplification (MLPA) analysis and sequence-specific differenzial PCR amplification of the CYP21A2 and CYP21A1P genes, using 4 pair-wise sequence-specific primers, followed by sequencing of the entire CYP21A2 gene. Large gene deletions were identified in 45 (31.3%) of the 144 unrelated CAH alleles, whereas the most frequent point mutations were intron 2 splice mutations (c.293-13A > G) (41/144, 28.5 %). The MLPA analysis successfully identified 23 of 72 patients (31.9%) with single copy deletion in CYP21A2. This paper describes a rapid and accurate method for the molecular diagnosis of 21-hydroxylase deficiency, which relies on the identification of point mutations and structural rearrangements within the CYP21A2 gene.