Department of Molecular Genetics Function and Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.
Clin Biochem. 2009 Sep;42(13-14):1363-7. doi: 10.1016/j.clinbiochem.2009.05.015. Epub 2009 Jun 6.
The purpose of this study was to identify and determine the frequencies of rare CYP21A2 gene mutations in patients with 21-hydroxylase deficiency (21-OHD) in the Cypriot population.
Direct sequencing and MLPA analysis of the CYP21A2 gene.
A group of families with 21-OHD were screened for the presence of rare CYP21A2 gene mutations. The rare V304M missense mutation was detected as compound heterozygous in two females with the nonclassical (NC) form of congenital adrenal hyperplasia (CAH). The rare F306insT was also detected in a female with severe salt wasting in the homozygous state and in cis in both alleles with the V281L mutation. Lastly, the rare A391T missense mutation was reported in a female patient with NC-CAH. A carrier rate of 2.1% for the V304M was also observed in a cohort of healthy controls.
The frequency of V304M mutation among Cypriots is high and the first reported so far and patients characterized as compound heterozygotes or heterozygotes are most readily identified by a mild phenotype of CAH. Thus, V304M should be included in the panel of mutations associated with the NC forms of 21-OHD.
本研究旨在鉴定和确定 CYP21A2 基因罕见突变在塞浦路斯人群中 21-羟化酶缺乏症（21-OHD）患者中的发生频率。
对 CYP21A2 基因进行直接测序和 MLPA 分析。
一组 21-OHD 家族被筛选是否存在罕见 CYP21A2 基因突变。两种非经典（NC）先天性肾上腺皮质增生（CAH）女性均为复合杂合子，检测到罕见的 V304M 错义突变。在纯合状态下，一位严重盐耗竭的女性和 V281L 突变的两个等位基因中均存在罕见的 F306insT，最后，在一位 NC-CAH 女性患者中报告了罕见的 A391T 错义突变。在一组健康对照中，还观察到 V304M 的携带者频率为 2.1%。
V304M 突变在塞浦路斯人中的频率较高，是迄今为止首次报道的突变，具有 CAH 轻度表型的复合杂合子或杂合子患者最容易被识别。因此，V304M 应包含在与 21-OHD 的 NC 形式相关的突变组中。
