Diagnosis, treatment and genetic analysis of 11β -hydroxylase deficiency caused by CYP11B gene mutation
Received date: 2022-07-28
Revised date: 2022-09-05
Online published: 2022-09-28
Congenital adrenal hyperplasia (CAH) is an autosomal recessive hereditary disease, and the 11β- hydroxylase deficiency is the second most common syndrome in different types of CAH. The occurrence of 11β- hydroxylase deficiency is related to the mutation of CYP11B gene on human autosome 8. In this report, we detected the gene mutation sites of a 14-year-old patient with 11β-hydroxylase deficiency by whole exon sequencing (WES), verified the suspected mutation by Sanger sequencing, and analyzed its characteristics. Gene sequencing revealed that homozygous missense mutation of c.1226C>T appeared on the 8th exon of CYP11B1 gene, which resulted in the mutation of the encoding protein Ser409 to phenylalanine (p. Ser409Phe), affecting the binding of heme and enzyme and resulting in the loss of CYP11B1 enzyme activity and a series of clinical symptoms. This mutation has not been reported at home and abroad. This case enriches the variation spectrum of CYP11B1 gene and provides clinical data and genetic resources for further research on the pathogenesis of 11β-hydroxylase deficiency.
Qingqing Song, Susu Zhang, Zhen Zhang, Jia Sun, Rui Yang, Jitong Li , Hong Chen . Diagnosis, treatment and genetic analysis of 11β -hydroxylase deficiency caused by CYP11B gene mutation[J]. Hereditas(Beijing), 2022 , 44(12) : 1175 -1182 . DOI: 10.16288/j.yczz.22-115
| [1] | Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med, 2015, 17(5): 405-424. |
| [2] | Zhao C, Xie XL, Ji WZ, Qi M, Zhou Q, Li MR, Li PN, Jiang YH, Zhang H. A review of consensus statements, practice resources, standards and guidelines for clinical applications of next-generation sequencing technologies in the United States. Chin J Med Genet, 2021, 38(6): 513-520. |
| [2] | 赵辰, 谢小雷, 冀维真, 祁鸣, 周青, 李孟蓉, 李培宁, 姜永辉, 张慧. 美国二代测序技术临床应用的共识声明、实践资源、技术标准和指南的概述. 中华医学遗传学杂志, 2021, 38(6): 513-520. |
| [3] | Wang XJ, Nie M, Sun ML. Molecular genetics research progress of 11β-hydroxylase deficiency. J Reprod Med, 2014, 23(2): 160-164. |
| [3] | 王晓晶, 聂敏, 孙梅励. 11β-羟化酶缺陷症遗传学研究现状. 生殖医学杂志, 2014, 23(2): 160-164. |
| [4] | Zhang HL, Zhang QJ, Lin G, Zhang C, Zhao J, Xie ZJ. 11β-hydroxylase deficiency caused by a duplication mutation of 23 basepairs:one case report. Chin J Endocrinol Metab, 2019, 35(7): 606-608. |
| [4] | 张慧玲, 张前军, 林戈, 张春, 赵娟, 谢忠建. 一例由23个碱基重复突变导致的11β-羟化酶缺陷病例报道. 中华内分泌代谢杂志, 2019, 35(7): 606-608. |
| [5] | White PC, Curnow KM, Pascoe L. Disorders of steroid 11 beta hydroxylase isozymes. Endocr Rev, 1992, 15(4): 421- 438. |
| [6] | Chinese Society of Endocrinology.Expert consensus on the diagnosis and treatment of primary aldosteronism (2020). Chin J Endocrinol Metab, 2020, 36(9): 727-736. |
| [6] | 中华医学会内分泌学分会. 原发性醛固酮增多症诊断治疗的专家共识(2020版). 中华内分泌代谢杂志, 2020, 36(9): 727-736. |
| [7] | Luo Y, He WW, Cheng QF, Yang SM, Du ZP, Mei M, Xu ZX, Hu JB, Wang KR, He YF, Li QF, Song Y. Re- evaluation of the diagnostic value and optimal cutoff point of captopril challenge test in diagnosis of primary aldosteronism. Chin J Intern Med, 2022, 61(1): 60-65. |
| [7] | 罗燕, 何文雯, 程庆丰, 杨淑敏, 杜志鹏, 梅玫, 徐智新, 胡金波, 王看然, 何一帆, 李启富, 宋颖. 卡托普利试验在原发性醛固酮增多症诊断中的价值及适宜切点的再评价. 中华内科杂志, 2022, 61(1): 60-65. |
| [8] | Wu W, Wang JL, Chen XQ, Chen XF, Wang XM, Liang XY, Dong GP. A case of 11β-hydroxylase deficiency caused by compound heterozygous mutation of CYP11B1 gene. Chin J Med Genet, 2016, 33(5): 738-740. |
| [8] | 吴蔚, 王金玲, 陈秀琴, 陈雪峰, 王秀敏, 梁心怿, 董关萍. CYP11B1基因复合杂合突变致11β-羟化酶缺乏症一例. 中华医学遗传学杂志, 2016, 33(5): 738-740. |
| [9] | White PC, Dupont J, New MI, Leiberman E, Hochberg Z, R?sler A. A mutation in CYP11B1 (Arg-448→His) associated with steroid 11β-hydroxylase deficiency in jews of Moroccan origin. J Clin Invest, 1991, 87(5): 1664-1667. |
| [10] | Geley S, Kapelari K, J?hrer K, Peter M, Glatzl J, Vierhapper H, Schwarz S, Helmberg A, Sippell WG, White PC, Kofler R. CYP11B 1 mutations causing congenital adrenal hyperplasia due to 11β hydroxylase deficiency. J Clin Endocrinol Metab, 1996, 81(8): 2896-2901. |
| [11] | Zhu YS, Cordero JJ, Can S, Cai LQ, You XK, Herrera C, DeFillo-Ricart M, Shackleton C, Imperato-McGinley J. Mutations in CYP11B1 gene: phenotype-genotype correlations. Am J Med Genet A, 2003, 122A(3): 193-200. |
| [12] | Liang K, Qing L, Liu FQ, Liu JB, Hou XG, Chen L. Male infertility caused by 21-hydroxylase deficiency with testicular adrenal gland tumor:one case report. Chin J Endocrinol Metab, 2018, 34(12): 1048-1051. |
| [12] | 梁凯, 卿立, 刘福强, 刘金波, 侯新国, 陈丽. 21-羟化酶缺陷症合并睾丸肾上腺残基瘤致男性不育一例报道. 中华内分泌代谢杂志, 2018, 34(12): 1048-1051. |
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号
