Kelestimur F, Everest H, Dundar M, Tanriverdi F, White C, Witchel S F
Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey.
Exp Clin Endocrinol Diabetes. 2009 May;117(5):205-8. doi: 10.1055/s-2008-1081209. Epub 2008 Oct 1.
The congenital adrenal hyperplasias (CAH) are a group of autosomal recessive disorders due to decreased activity of the enzymes responsible for cortisol biosynthesis. Since CYP21 gene mutations in non-classical CAH (NC-CAH) due to 21-hydroxylase deficiency among Turkish women have not been well characterized, we performed CYP21 genotype analyses to determine the frequency of specific mutations in our population.
Clinical study in women with hyperandrogenism at Endocrinology Department of a University Hospital. The CYP21 genotype analysis was performed at the Children's Hospital of Pittsburgh.
The study population included 32 Turkish women with hyperandrogenism and hirsutism, 5 patients with NC-CAH due to 21-hydroxylase deficiency and their 3 first degree relatives. The following steroids were measured: cortisol, prolactin, DHEAS, free testosterone, testosterone, LH, FSH, estradiol, 17-OHP, 11-deoxycortisol, and androstenedione. The ACTH stimulation test was performed in the follicular phase of the menstrual cycle. CYP21 mutations were detected by CYP21 specific PCR followed by allele specific restriction fragment length polymorphism (RFLP) or single strand conformational polymorphism analyses.
Among hirsute Turkish women with hyperandrogenemia 21.9% was heterozygous carriers of CYP21 mutations; all had basal and stimulated 17-OHP values within the normal range. Alleles detected were as follows: Q318X, V281L, del/gene conversion, and R356W. Thus, 21.9% of women were heterozygous CYP21 carriers.
The frequency of CYP21 heterozygosity is high among Turkish women with hirsutism and hyperandrogenism. Women with hyperandrogenism who are heterozygous CYP21 mutation carriers have normal basal and stimulated 17-OHP levels. In other words, normal basal and ACTH-stimulated 17-OHP responses do not exclude heterozygosity for CYP21 mutations. The molecular differences between symptomatic carriers, e.g., our patients and asymptomatic CYP21 mutations carriers, e.g., mothers of children with classical CAH, remain to be elucidated.
先天性肾上腺皮质增生症（CAH）是一组常染色体隐性疾病，由负责皮质醇生物合成的酶活性降低所致。由于土耳其女性中因21 - 羟化酶缺乏导致的非经典型CAH（NC - CAH）患者的CYP21基因突变尚未得到充分研究，我们进行了CYP21基因分型分析，以确定我们人群中特定突变的频率。
在一所大学医院内分泌科对高雄激素血症女性进行的临床研究。CYP21基因分型分析在匹兹堡儿童医院进行。
研究人群包括32名患有高雄激素血症和多毛症的土耳其女性、5名因21 - 羟化酶缺乏导致的NC - CAH患者及其3名一级亲属。检测了以下类固醇激素：皮质醇、催乳素、硫酸脱氢表雄酮、游离睾酮、睾酮、促黄体生成素、促卵泡生成素、雌二醇、17 - 羟孕酮、11 - 脱氧皮质醇和雄烯二酮。在月经周期的卵泡期进行促肾上腺皮质激素（ACTH）刺激试验。通过CYP21特异性聚合酶链反应（PCR）检测CYP21突变，随后进行等位基因特异性限制性片段长度多态性（RFLP）或单链构象多态性分析。
在患有高雄激素血症的多毛土耳其女性中。21.9%是CYP21突变的杂合携带者；她们的基础和刺激后的17 - 羟孕酮值均在正常范围内。检测到的等位基因如下：Q318X、V281L、缺失/基因转换和R356W。因此，21.9%的女性是CYP21杂合携带者。
在患有多毛症和高雄激素血症的土耳其女性中，CYP21杂合子的频率较高。CYP21突变杂合携带者的高雄激素血症女性基础和刺激后的17 - 羟孕酮水平正常。换句话说，基础和ACTH刺激后的17 - 羟孕酮反应正常并不能排除CYP21突变的杂合性。有症状携带者（如我们的患者）与无症状CYP21突变携带者（如经典型CAH患儿的母亲）之间的分子差异仍有待阐明。
