Genotype and hormonal phenotype in nonclassical 21-hydroxylase deficiency.
Genotype and hormonal phenotype in nonclassical 21-hydroxylase deficiency.
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DOI：
10.1210/jcem-64-1-86
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发表时间：
1987
期刊：
影响因子：
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通讯作者：
P. Speiser;M. New
中科院分区：
文献类型：
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作者：
P. Speiser;M. New
在非经典类固醇21-羟化酶缺乏症中，基因型可以表现为21-羟化酶缺陷的纯合子轻度（非经典）形式，或者表现为复合杂合子，具有一个重度（经典）和一个轻度（非经典）21-羟化酶缺乏症等位基因。我们研究了非经典21-羟化酶缺乏症患者的激素水平，在这些患者中，系谱分析和/或HLA连锁不平衡允许明确鉴定各自的单倍型为经典或非经典。结果表明，复合杂合子（21-OH缺乏/21-OH缺乏轻度）的ACTH刺激的17-羟孕酮（17-OHP）反应显著大于轻度纯合子（21-OH defmild/21-OH defmild）：60 min时，各组分别为8，131 +/-4，205（+/-SD）（n = 17）和4，468 +/-2，123 ng/dl（n = 31）（P小于或等于0.01）; 360 min时，11，067 +/-5，582（n = 17）vs. 5746 +/- 1565（n = 8，P小于或等于0.01）。由于两组的血清皮质醇水平相同，因此前一组的17-OHP与皮质醇的比值较高。60分钟ACTH刺激的血清δ 4-雄烯二酮水平也显着高于复合杂合子比轻度纯合子。血清脱氢表雄酮及其硫酸盐在两组间无显著性差异。值得注意的是，复合杂合子并不比轻度基因缺陷的纯合子更可能有雄激素过多的迹象。经典（21-OH缺乏/21-OH正常）和非经典（21-OH缺乏/21-OH正常）21-羟化酶缺乏等位基因的杂合子之间，血清17-OHP、17-OHP/皮质醇、δ 4-雄烯二酮和脱氢表雄酮及其硫酸盐的刺激水平没有显着差异。因此，一个单一的正常21-羟化酶等位基因的存在足以掩盖一个严重的和一个轻度的21-羟化酶缺陷等位基因之间的差异对相反的单倍型。我们的结论是，作为一个组的复合杂合子患者有一个显着较高的反应，21-羟化酶前体促肾上腺皮质激素刺激比纯合子轻度21-羟化酶缺乏状态的患者。
In nonclassical steroid 21-hydroxylase deficiency, the genotype may be represented as a homozygous mild (nonclassical) form of the 21-hydroxylase defect or as a compound heterozygote, with one severe (classical) and one mild (nonclassical) 21-hydroxylase deficiency allele. We examined hormone levels in patients with nonclassical 21-hydroxylase deficiency in whom pedigree analysis and/or HLA linkage disequilibrium allowed unequivocal identification of the respective haplotypes as either classical or nonclassical. The results indicated that compound heterozygotes (21-OH defsevere/21-OH defmild) have an ACTH-stimulated 17-hydroxyprogesterone (17-OHP) response significantly greater than that of mild homozygotes (21-OH defmild/21-OH defmild): at 60 min, 8,131 +/- 4,205 (+/-SD) (n = 17) vs. 4,468 +/- 2,123 ng/dl (n = 31) for the respective groups (P less than or equal to 0.01); at 360 min, 11,067 +/- 5,582 (n = 17) vs. 5746 +/- 1565 (n = 8, P less than or equal to 0.01). Since serum cortisol levels were the same in both groups, the ratio of 17-OHP to cortisol was higher in the former group. Sixty minute ACTH-stimulated serum delta 4-androstenedione levels also were significantly higher in compound heterozygotes than in mild homozygotes. Serum dehydroepiandrosterone and its sulfate were not significantly different between the two groups. Notably, compound heterozygotes were no more likely to have signs of androgen excess than were homozygotes for the mild gene defect. Stimulated levels of serum 17-OHP, 17-OHP/cortisol, delta 4-androstenedione and dehydroepiandrosterone and its sulfate did not differ significantly between heterozygotes for the classical (21-OH defsevere/21-OHnormal) and nonclassical (21-OH defmild/21-OHnormal) 21-hydroxylase deficiency alleles. Thus, the presence of a single normal 21-hydroxylase allele is sufficient to obscure the difference between a severe and a mild 21-hydroxylase deficiency allele on the opposite haplotype. We conclude that the compound heterozygous patients as a group have a significantly higher response of 21-hydroxylase precursors to ACTH stimulation than do patients with the homozygous mild 21-hydroxylase deficiency state.