PDF(1471 KB)
Analysis of CYP21A2 gene mutation in one case of congenital adrenal hyperplasia
LIN Xiao-Mei, WU Ben-Qing, HUANG Jin-Jie, LI Bo, FAN Yi, LIN Lin-Hua, YAO Qiu-Xuan, WU Wen-Yuan, YU Lian
Chinese Journal of Contemporary Pediatrics ›› 2013, Vol. 15 ›› Issue (11) : 942-947.
PDF(1471 KB)
PDF(1471 KB)
Analysis of CYP21A2 gene mutation in one case of congenital adrenal hyperplasia
CYP21A2 gene mutations in a child with congenital adrenal hyperplasia (CAH), and the child's parents, were detected in the study. The clinical features, treatment monitoring and molecular genetic mechanism of CAH are reviewed. In the study, DNA was extracted from peripheral blood samples using the QIAGEN Blood DNA Mini Kit; a highly specific PCR primer for CYP21A2 gene was designed according to the sequence difference between CYP2lA2 gene and its pseudogene; the whole CYP2lA2 gene was amplified with PrimeSTAR DNA polymerase (Takara), and the amplification product was directly sequenced to detect and analyze CYP2lA2 gene mutation. The child was clinically diagnosed with CAH (21-hydroxylase deficiency, 21-OHD) at the age of 36 days, and the case was confirmed by genetic diagnosis at the age of 1.5 years. The proband had a homozygous mutation at c.293-13C in the second intron of CYP21 gene, while the parents had heterozygous mutations. Early diagnosis and standard treatment of CAH (21-OHD) should be performed to prevent salt-wasting crisis and reduce mortality; bone aging should be avoided to increase final adult height (FAH), and reproductive dysfunction due to oligospermia in adulthood should be avoided. These factors are helpful for improving prognosis and increasing FAH. Investigating the molecular genetic mechanism of CAH can improve recognition and optimize diagnosis of this disease. In addition, carrier diagnosis and genetic counseling for the proband family are of great significance.
Congenital adrenal hyperplasia / Steroid 21-hydroxylase / Point mutation / Child
[1] Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline[J]. J Clin Endocrinol Metab, 2010, 95(9): 4133-4160.
[2] Krone N, Dhir V, Ivison HE, Arlt W. Congenital adrenal hyperplasia and P450 oxidoreductase deficiency[J]. J Clin Endocrinol, 2007, 66(2): 162-172.
[3] 颜纯.小儿内分泌学 [M].北京:人民卫生出版社, 2006: 216239.
[4] 吴本清. 新生儿危重症监护诊疗与护理 [M].北京: 人民卫生出版社, 2009: 223-226.
[5] Ji C, Huang XW, Yang RW, Wang X, Zhao ZY. Gonadotropins and sex Hormons in Healthy Chinese infants[J]. Indian Pediatr, 2008, 45(6): 489-492.
[6] 郭辉, 闵娟, 毛维玉, 林琳华, 吴本清, 何林.出生后采血时间对新生儿CAH筛查结果的影响分析[J].国际医药卫生导报, 2007, 13(10): 34-36.
[7] 首都儿科研究所, 九市儿童体格发育调查协作组. 中国七岁以下儿童体重、身长／身高和头围的生长标准值及标准化生长曲线[J]. 中华儿科杂志, 2009, 47(3): 173-178.
[8] Nimkarn S, New MI. Gene ReviewsTM: 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia[EB/OL]. University of Washington, Seattle; 1993-2002 Feb 26 [updated Aug 24, 2010].
[9] 肖慧文, 马华梅. 先天性肾上腺皮质增生症21-羟化酶缺乏患者的生长与最终身高影响因素[J]. 国际儿科学杂志, 2011, 38(3): 210-215.
[10] 杜敏联. 先天性肾上腺皮质增生症的青春发育和治疗进展[J].临床儿科杂志, 2008, 26(12): 1006-1009.
[11] Claahsen-van der Grinten HL, Stikkelbroeck NM, Sweep CG, Hermus AR, Otten BJ. Fertility in patients with congenital adrenal hyperplasia [J]. J Pediatr Endocrinol Metab, 2006, 19 (5): 677-685.
[12] Speiser PW, White PC. Congenital adrenal hyperplasia[J]. N Engl J Med, 2003, 349(8): 776-788.
[13] 肖慧文, 马华梅, 苏喆, 杜敏联, 李燕虹, 陈红珊, 等.血清类固醇检测于先天性肾上腺皮质增生症治疗监测意义的评价[J]. 中华儿科杂志, 2012, 50(4): 301-307．
[14] Charmandari E, Matthews DR, Johnston A, Brook CG, Hindmarsh PC. Serum cortisol and 17hydroxyprogesterone interrelation in classic 21-hydroxylase deficiency: is current replacement therapy satisfactory?[J]. J Clin Endocrinol Metab, 2001, 86(10): 4679-4685.
[15] Migeon CJ, Wisniewski AB. Congenital adrenal hypevplasia owing to 21-hydroxylase deficiency. Growth, development, and therapeutic considerations[J]. Endocrinol Metab Clin North Am, 2001, 30(1): 193-206.
[16] Eugster EA, Dimeglio LA, Wright JC, Freidenberg GR, Seshadri R, Pescovitz OH. Height outcome in congenital adrenal hyperplasia caused by 21-Hydroxylase deficiency: a meta-analysis[J]. J Pediatr, 2001, 138(1): 26-32.
[17] Einaudi S, Lala R, Corrias A, Matarazzo P, Pagliardini S, de Sanctis C.Auxological and biochemical parameters in assessing treatment of infants and toddlers with congenital adrenal hyperplasia due to 21-hydroxylase deficiency[J].J Pediatr Endocrinol, 1993, 6(2): 173-178.
[18] Owerbah D, Crawford YM, Draznin MB. Direct anatysis Of CYP21B gencs in 2l-hydroxylase deficiency using polymerase chain reaclion amphflcation[J]. Mol Endocrinol, 1990, 4(1): 125-131.
[19] White PC, New MI, Dupont B. Structure Of human steroid 21-hydroxyiase genes[J]. Proc Natl Acad Sci USA, 1986, 83(14): 5111-5115.
[20] Higashi Y, Tanae A, Inoue H, Hiromasa T, Fujii-Kuriyama Y.Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: possible gene conversion products[J]. Proc Natl Acad Sci U S A, 1988, 85(20): 7486-7490.
[21] Janjanin N, Dumic M, Skrabic V, Kusec V, Grubic Z, Spehar Uroic A.Five patient with congenital adrenal hyperplasia duo to 21-hydroxylase deficiency (one with associated neuroblastoma) discovered in three generations of one family[J]. Horm Res, 2007, 67(3):111-116.
