Rabbani Bahareh, Mahdieh Nejat, Ashtiani Mohammad Tahgi Haghi, Larijani Bagher, Akbari Mohammad Taghi, New Maria, Parsa Alan, Schouten Jan P, Rabbani Ali
Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Genet Test Mol Biomarkers. 2012 Feb;16(2):82-90. doi: 10.1089/gtmb.2011.0099. Epub 2011 Oct 21.
Defects in the CYP21A2 gene cause steroid 21-hydroxylase deficiency, which is the most frequent cause of congenital adrenal hyperplasia. Forty four affected families were investigated to identify the mutation spectrum of the CYP21A2 gene.
Families were subjected to clinical, biochemical, and molecular analyses. Allele-specific polymerase chain reaction amplification was used for eight common mutations followed by dosage analysis to exclude CYP21A2 deletions.
The most frequent mutations detected were gene deletions and chimera (31.8%). Other mutation frequencies were as follows: Q318X, 15.9%; I2G, 14.8%; I172N, 5.8%; gene duplication, 5.7%; R356W, 8%; and E6 cluster mutations, 2.3%. Direct sequencing of the CYP21A2 gene revealed R316X, P453S, c.484insT, and a change at the start codon. Different modules carried by patients were classified into five different haplotypes. The genotype phenotype correlation (positive predictive value) for group null, A, B, and C were 92.3%, 85.7%, 100%, and 0, respectively.
Methods used will be helpful for carrier detection and antenatal diagnosis, especially with inclusion of the multiplex ligation probe dependent amplification technique, which is easier for routine tests in comparison with other methods. Mutation frequencies indicate that Iranians are possible descendants of Asians and Europeans.
CYP21A2基因突变导致类固醇21-羟化酶缺乏，这是先天性肾上腺皮质增生最常见的病因。对44个患病家庭进行了调查，以确定CYP21A2基因的突变谱。
对家庭进行临床、生化和分子分析。采用等位基因特异性聚合酶链反应扩增检测8种常见突变，随后进行剂量分析以排除CYP21A2基因缺失。
检测到的最常见突变是基因缺失和嵌合体（31.8%）。其他突变频率如下：Q318X，15.9%；I2G，14.8%；I172N，5.8%；基因重复，5.7%；R356W，8%；E6簇突变，2.3%。CYP21A2基因直接测序揭示了R316X、P453S、c.484insT以及起始密码子处的改变。患者携带的不同模块被分为五种不同的单倍型。无效组、A组、B组和C组的基因型-表型相关性（阳性预测值）分别为92.3%、85.7%、100%和0。
所采用的方法将有助于携带者检测和产前诊断，尤其是采用多重连接探针依赖扩增技术，与其他方法相比，该技术更易于常规检测。突变频率表明伊朗人可能是亚洲人和欧洲人的后裔。
