11β-羟化酶缺陷症临床和基因型分析  

Clinical and genetic analysis of 11β-hydroxylase deficiency

作　　者：孙首悦[1] 张曼娜[1] 杨军[1] 张惠杰[1] 刘建民[1] 洪洁[1] 宁光[1] 李小英[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院内分泌代谢科上海市内分泌代谢病临床医学中心上海市内分泌代谢病研究所,200025

出　　处：《中华医学杂志》2011年第42期2999-3002,共4页National Medical Journal of China

基　　金：上海市科委科研基金（09DJ1400402）

摘　　要：目的分析2例11β-羟化酶缺陷症（11β-OHD）患者的临床特点及分子遗传学诊断。方法收集2例患者临床、基础激素测定和影像学检查资料，并采用PCR产物直接测序方法明确CYP11B1基因突变结果2例患者分别因“青少年高血压伴肾上腺肿瘤”和“先天性尿道下裂伴高血压17年、周期性血尿3个月”入院；激素测定示：促肾上腺皮质激素、17-羟孕酮、11-去氧皮质醇、雄烯二酮和睾酮高于正常，而血钾、醛固酮和肾素活性偏低。双侧肾上腺呈结节样增生。筛查CYP11B1基因，证实患者1为该基因8号外显子第453位和第454位氨基酸的复合杂合替代突变（R453Q／R454C）；而患者2为该基因第454位氨基酸纯合替代突变（R454C）。结论11β-OHD是引起先天性肾上腺皮质增生的第二大类病因，易误诊为原发性醛固酮增多症、21-羟化酶缺陷症等在青少年起病的难治性高血压伴有双侧肾上腺皮质增生的患者中，应该注意11β-OHD的筛查。Objective To explore the clinical and genetic characteristics of two patients with 116- hydroxylase deficiency （ 11β-OHD）. Methods The clinical features and laboratory data were collected from the patients and their families. All exons of CYPllB1 gene were amplified by PCR. And the PCR product sequences were identified by a DNA analyzer. Results Two patients presented with juvenile hypertension with bilateral adrenal hyperplasia and congenital hypospadias, hypertension for 17 years and periodic hematuria for 3 months after dexamethasone therapy respectively. Steroid analysis showed the typical pattern of 11β-OHD ： elevated plasma levels of adrenocorticotropic hormone （ ACTH ） , 17-hydroxyprogesterone （17OHP）, 11-deoxycortisol, androstenedione and testosterone and lowered levels of potassium, aldosterone and plasma renin activity （PRA）. CT scan revealed the presence of bilateral nodular hyperplasia of adrenal glands. Sequencing analysis showed compound heterozygous mutations of [ R453Q] ＋ [ R454C] at exon 8 in patient 1 and homozygous mutation of [ R454C ] at exon 8 in patient 2. Conclusion 11β-OHD is the second major cause of congenital adrenal hyperplasia. The classic characteristics are hypertension with low a level of PRA, hypokalemia, female pseudohermaphrodism and male sexual precocity. 11β-OHD should be screened in the patients with juvenile onset hypertension accompanied by bilateral adrenal hyperplasia.

关 键 词：类固醇11β-羟化酶 基因突变 CYP11B1基因 肾上腺增生 先天性 

分 类 号：R586[医药卫生—内分泌]