氯离子电压门控通道2（CLCN2）基因突变导致青少年原发性醛固酮增多症1例

A case of primary aldosteronism in adolescence caused by a mutation in the chloride voltage-gated channel 2（CLCN2）gene

摘要

患者，男，16岁，因“体检发现血压高16 d”入院，患者入院前16 d在学校体检时发现血压高，当时测血压156/107 mmHg。入院查体无阳性体征，查血钾2.98 mmol/L，查醛固酮卧立位试验及卡托普利试验阳性，皮质醇节律、血儿茶酚胺、四肢同步血压、双肾上腺CT未见异常。而后基因检测发现，氯离子电压门控通道2（CLCN2）基因突变，给予氨氯地平、螺内酯药物治疗，血压及血钾得以控制。

Abstract

A 16-year-old male was admitted due to elevated blood pressure detected during physical examination for 16 days. Sixteen days prior to admission, hypertension was identified during a school physical examination, with a recorded blood pressure of 156/107 mmHg. Physical examination upon admission revealed no positive signs. Laboratory findings showed a serum potassium level of 2.98 mmol/L. The aldosterone suppression tests (upright and supine positions) and captopril challenge test were positive. Cortisol rhythm, plasma catecholamines, four-limb synchronous blood pressure measurements, and bilateral adrenal CT were unremarkable. Subsequent genetic testing revealed a mutation in the chloride voltage-gated channel 2（CLCN2）gene. The patient was treated with amlodipine and spironolactone, achieving controlled blood pressure and serum potassium levels.

关键词

高血压 / 低钾血症 / 原发性醛固酮增多症 / 氯离子电压门控通道2(CLCN2)

Key words

hypertension / hypokalemia / primary aldosteronism / chloride voltage-gated channel 2 (CLCN2)

参考文献

[1] Sang X, Jiang Y, Wang W, et al. Prevalence of and risk factors for primary aldosteronism among patients with resistant hypertension in China[J]. J Hypertens, 2013, 31(7): 1465-1471.

[2] 国家卫生健康委高血压诊疗研究重点实验室学术委员会 . 高血压患者中原发性醛固酮增多症检出、诊断和治疗的指导意见[J]. 中华高血压杂志, 2021, 29(6): 508-518.

[3] Xu Z, Yang J, Hu J, et al. Primary aldosteronism in patiengts in China with recengtly detected hypertension[J]. J Am Coll Cardiol, 2020, 75(16): 1913-1922.

[4] Thomas RM, Ruel E, Shantavasinkul PC, et al. Endocrine hypertension: an overview on the current etiopathogenesis and management options[J]. World J Hypertens, 2015, 5(2): 14-27.

[5] Young WF . Diagnosis and treatment of primary aldosteronism: practical clinical perspectives[J]. J Intern Med, 2019, 285(2): 126-148.

[6] Stowasser M, Gordon RD, Tunny TJ, et al. Familial hyperaldosteronism type Ⅱ: five families with a new variety of primary aldosteronism[J]. Clin Exp Pharmacol Physiol, 1992, 19(5): 319-322.

[7] Wang HP, Tong AL . Research progress on gene mutation related primary aldosteronism[J]. Int J Endocrinol Met, 2021, 41(2): 87-90.

[8] So A, Duffy DL, Gordon RD, et al. Familial hyperaldosteronism type Ⅱ is linked to the chromosome 7p22 region but also shows predicted heterogeneity[J]. J Hypertens, 2005, 23(8): 1477-1484.

[9] Scholl UI, Stölting G, Schewe J, et al. CLCN2 chloride channel mutations in familial hyperaldosteronism type Ⅱ[J]. Nat Genet, 2018, 50(3): 349-354.

[10] Dutta RK, Arnesen T, Heie A, et al. A somatic mutation in CLCN2 identified in a sporadic aldosterone-producing adenoma[J]. Eur J Endocrinol, 2019, 181(5): K37-K41.

[11] Rege J, Nanba K, Blinder AR, et al. Identification of somatic mutations in CLCN2 in aldosterone-producing adenomas[J]. J Endocr Soc, 2020, 4(10): bvaa123.

[12] Göppner C, Orozco IJ, Hoegg-Beiler MB, et al. Pathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism[J]. Nat Commun, 2019, 10(1): 4678.

[13] Schewe J, Seidel E, Forslund S, et al. Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation[J]. Nat Commun, 2019, 10(1): 5155.

[14] Hu C, Rusin CG, Tan Z, et al. Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electrical oscillators[J]. J Clin Invest, 2012, 122(6): 2046-2053.

[15] Depienne C, Bugiani M, Dupuits C, et al. Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study[J]. Lancet Neurol, 2013, 12(7): 659-668.

[16] Dutta RK, Söderkvist P, Gimm O . Genetics of primary hyperaldosteronism[J]. Endocr Relat Cancer, 2016, 23(10): R437-454.

[17] Mulatero P, Tizzani D, Viola A, et al. Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (primary aldosteronism in torino-genetic forms)[J]. Hypertension, 2011, 58(5): 797-803.

[18] Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline[J]. J Clin Endocrinol Metab, 2016, 101(5): 1889-1916.

[19] 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(2024版)[J]. 中华内分泌代谢杂志, 2025, 41(1): 12-24.

[20] 周俊, 朱佳雯, 王铖, 等 . 人类新生突变的起源、特征及其对子代健康的影响[J]. 中国细胞生物学学报, 2024, 46(4): 865-879.

[21] Lejeune J, Gautier M, Turrpin R . Study of somatic chromosomes from 9 Mongoloid children[J]. C R Hebd Seances Acad Sci, 1959, 248(11): 1721-1722.

[22] Sasani TA, Pedersen BS, Gao Z, et al. Large, three-generation human families reveal post-zygotic mosaicism and variability in germline mutation accumulation[J]. ELife, 2019, 8: e46922.

基金资助

国家自然科学基金(32260214)

江西省科技厅应用研究培育（临床医学领域）(20212BAG70030)