正常血镁Gitelman综合征1例的临床表现及基因诊断分析

doi:10.3969/j.issn.1674-8115.2022.02.019

上海交通大学学报(医学版) ›› 2022, Vol. 42 ›› Issue (2): 253-258.doi: 10.3969/j.issn.1674-8115.2022.02.019

• 病例报告 • 上一篇

正常血镁Gitelman综合征1例的临床表现及基因诊断分析

周建华(), 李晓华, 张宏利()

上海中医药大学附属第七人民医院内分泌代谢科，上海 200137

收稿日期:2021-08-19 出版日期:2022-02-28 发布日期:2022-03-17
通讯作者: 张宏利 E-mail:642135341@qq.com;hongliting@sina.com
作者简介:周建华（1981—），女，主治医师，硕士；电子信箱：642135341@qq.com。
基金资助:
海派石氏伤科中医流派浦东基地工作室建设(PDZY-2019-0705)

Clinical manifestation and gene diagnosis of Gitelman syndrome with normal blood magnesium in 1 case

Jianhua ZHOU(), Xiaohua LI, Hongli ZHANG()

Department of Endocrinology and Metabolism, the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China

Received:2021-08-19 Online:2022-02-28 Published:2022-03-17
Contact: Hongli ZHANG E-mail:642135341@qq.com;hongliting@sina.com
Supported by:
Studio Construction of Pudong Base of Shanghai Traumatology Traditional Chinese Medicine School(PDZY-2019-0705)

摘要/Abstract

摘要：

目的·分析1例正常血镁Gitelman综合征患者的临床特点及其SLC12A3基因的突变特点。方法·以1例拟诊断为Gitelman综合征的患者为研究对象，分析其临床表现及辅助检查结果，并行SLC12A3基因和CLCNKB基因检测以明确诊断。结果·该患者成年起病，临床表现为低血钾、正常血镁、低尿钙，排除长期使用噻嗪类利尿剂、泻药，慢性腹泻和呕吐可能，诊断为Gitelman综合征。采用Sanger直接测序法，在SLC12A3基因检测到致病突变c.1084G>A和c.1850G>A，均被证实是新发现的突变位点。结论·基因检测有助于早期明确诊断Gitelman综合征并改善其预后。

关键词: Gitelman综合征, 低钾血症, SLC12A3基因

Abstract:

Objective·To analyze the clinical characteristics and SLC12A3 gene mutation of a patient with normal blood magnesium Gitelman syndrome.

Methods·A patient with Gitelman syndrome was studied. The clinical manifestations and auxiliary examination results were analyzed, and SLC12A3 gene and CLCNKB gene were detected to make a definite diagnosis.

Results·The patient developed into an adult with clinical manifestations of low blood potassium, normal blood magnesium and low urinary calcium. The possibility of long-term use of thiazide diuretics, laxatives, chronic diarrhea and vomiting was ruled out, and Gitelman syndrome was diagnosed. The pathogenic mutations c.1084G>A and c.1850G>A in SLC12A3 gene were detected by Sanger direct sequencing, which were confirmed to be the new mutation sites found in this study.

Conclusion·Gene detection is helpful to early diagnosis of Gitelman syndrome and improves its prognosis.

Key words: Gitelman syndrome, hypokalemia, SLC12A3 gene

中图分类号:

R692.6

周建华, 李晓华, 张宏利. 正常血镁Gitelman综合征1例的临床表现及基因诊断分析[J]. 上海交通大学学报(医学版), 2022, 42(2): 253-258.

Jianhua ZHOU, Xiaohua LI, Hongli ZHANG. Clinical manifestation and gene diagnosis of Gitelman syndrome with normal blood magnesium in 1 case[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2022, 42(2): 253-258.

图/表 5

图1 双手双能CT

Fig 1 Dual energy CT of hands

图2 SLA12A3 基因外显子8检测到的致病突变c.1084G>ANote： A. Heterozygous variation of SLA12A3 gene in proband. B. Wild type SLA12A3 gene of proband's father. C. Heterozygous variation of SLA12A3 gene carried by proband's mother.

Fig 2 Pathogenic mutation c.1084G>A detected in exon 8 of SLA12A3 gene

图3 SLA12A3 基因外显子15检测到的致病突变c.1850A>GNote： A. Heterozygous variation of SLA12A3 gene in proband. B. Heterozygous variation of SLA12A3 gene carried by proband's father. C. Wild type SLA12A3 gene of proband's mother.

Fig 3 Pathogenic mutation c.1850A>G detected in exon 15 of SLA12A3 gene

图4 预测NCCT突变的拓扑定位Note： Arrows indicate the position of the selected mutations.

Fig 4 Predicted topological localization of NCCT mutations

图5 蛋白质结构预测图Note： A. Wild type. B. Mutated type.

Fig 5 Predicted structure of the protein

参考文献 30

1	陈楠. Gitelman综合征: 早期诊断, 早期治疗[J]. 中华内科杂志, 2017, 56(9): 639-640.
2	BLANCHARD A, BOCKENHAUER D, BOLIGNANO D, et al. Gitelman syndrome: consensus and guidance from a kidney disease: improving global outcomes (KDIGO) controversies conference[J]. Kidney Int, 2017, 91(1): 24-33.
3	VARGAS-POUSSOU R, DAHAN K, KAHILA D, et al. Spectrum of mutations in Gitelman syndrome[J]. J Am Soc Nephrol, 2011, 22(4): 693-703.
4	JIANG L, CHEN C, YUAN T, et al. Clinical severity of Gitelman syndrome determined by serum magnesium[J]. Am J Nephrol, 2014, 39(4): 357-366.
5	AYUK J, GITTOES N J. How should hypomagnesaemia be investigated and treated[J]. Clin Endocrinol (Oxf), 2011, 75(6): 743-746.
6	VIERING D H H M, DE BAAIJ J H F, WALSH S B, et al. Genetic causes of hypomagnesemia, a clinical overview[J]. Pediatr Nephrol, 2017, 32(7): 1123-1135.
7	DIMKE H, MONNENS L, HOENDEROP J G, et al. Evaluation of hypomagnesemia: lessons from disorders of tubular transport[J]. Am J Kidney Dis, 2013, 62(2): 377-383.
8	TSENG M H, YANG S S, HSU Y J, et al. Genotype, phenotype, and follow-up in Taiwanese patients with salt losing tubulopathy associated with SLC12A3 mutation[J]. J Clin Endocrinol Metab, 2012, 97(8): E1478- E1482.
9	MA J, REN H, LIN L, et al. Genetic features of Chinese patients with Gitelman syndrome: sixteen novel SLC12A3 mutations identified in a new cohort[J]. Am J Nephrol, 2016, 44(2): 113-121.
10	LIU T, WANG C, LU J, et al. Genotype/phenotype analysis in 67 Chinese patients with Gitelman's syndrome[J]. Am J Nephrol, 2016, 44(2): 159-168.
11	WANG F, SHI C, CUI Y, et al. Mutation profile and treatment of Gitelman syndrome in Chinese patients[J]. Clin Exp Nephrol, 2017, 21(2): 293-299.
12	ZHAO Z, PEI Y, HUANG X, et al. Novel TRPM6 mutations in familial hypomagnesemia with secondary hypocalcemia[J]. Am J Nephrol, 2013, 37(6): 541-548.
13	NIJENHUIS T, VALLON V, van der KEMP A W, et al. Enhanced passive Ca²⁺ reabsorption and reduced Mg²⁺ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia[J]. J Clin Investig, 2005, 115(6): 1651-1658.
14	LIN S H, CHENG N L, HSU Y J, et al. Intrafamilial phenotype variability in patients with Gitelman syndrome having the same mutations in their thiazide-sensitive sodium/chloride cotransporter[J]. Am J Kidney Dis, 2004, 43(2): 304-312.
15	TOSI F, BIANDA N D, TRUTTMANN A C, et al. Normal plasma total magnesium in Gitelman syndrome[J]. Am J Med, 2004, 116(8): 573-574.
16	GRAZIANI G, FEDELI C, MORONI L, et al. Gitelman syndrome: pathophysiological and clinical aspects[J]. QJM, 2010, 103(10): 741-748.
17	MAIOLINO G, PAGNIN E, PLEBANI M, et al. Uric acid and cardiovascular-renal disease risk. Insights from a human model opposite to hypertension[J]. Int J Cardiol, 2016, 212: 18-19.
18	BOUCHIREB K, BOYER O, MANSOUR-HENDILI L, et al. Fanconi syndrome and severe polyuria: an uncommon clinicobiological presentation of a Gitelman syndrome[J]. BMC Pediatr, 2014, 14: 201.
19	GANGULI A, VEIS J H. Hyponatremia: a rare complication of Gitelman's syndrome[J]. Indian J Nephrol, 2017, 27(1): 74-77.
20	HAGOS Y, STEIN D, UGELE B, et al. Human renal organic anion transporter 4 operates as an asymmetric urate transporter[J]. J Am Soc Nephrol, 2007, 18(2): 430-439.
21	LI C C, ZHOU X L, HAN W X, et al. Identification of two novel mutations in SLC12A3 gene in two Chinese pedigrees with Gitelman syndrome and review of literature[J]. Clin Endocrinol (Oxf), 2015, 83(6): 985-993.
22	李宗跃, 徐潮, 高聆. Gitelman综合征分子遗传学研究进展[J].中华内分泌代谢杂志, 2020, 4(36): 348-351.
23	ZENG Y, LI P, FANG S, et al. Genetic analysis of SLC12A3 gene in Chinese patients with Gitelman syndrome[J]. Med Sci Monit, 2019, 25: 5942-5952.
24	BOUWER S T, COTO E, SANTOS F, et al. The Gitelman syndrome mutation, IVS9+1G>T, is common across Europe[J]. Kidney Int, 2007, 72(7): 898.
25	GAMBA G. The thiazide-Sensitive Na⁺-Cl^- cotransporter: molecular biology, functional properties, and regulation by WNKs[J]. Am J Physiol Renal Physiol, 2009, 297(4): F838-F848.
26	ROSENBAEK L L, ASSENTOFT M, PEDERSEN N B, et al. Characterization of a novel phosphorylation site in the sodium-chloride cotransporter, NCC[J]. J Physiol, 2012, 590(23): 6121-6139.
27	TUTAKHEL O A Z, BIANCHI F, SMITS D A, et al. Dominant functional role of the novel phosphorylation site S811 in the human renal NaCl cotransporter[J]. FASEB J, 2018, 32(8): 4482-4493.
28	LUO J, YANG X, LIANG J, et al. A pedigree analysis of two homozygous mutant Gitelman syndrome cases[J]. Endocr J, 2015, 62(1): 29-36.
29	VERHAVE J C, BECH A P, WETZELS J F, et al. Hepatocyte nuclear factor 1β-associated kidney disease: more than renal cysts and diabetes[J]. J Am Soc Nephrol, 2016, 27(2): 345-353.
30	LUO J W, MENG X R, YANG X, et al. Analysis of mutations of two Gitelman syndrome family SLC12A3 genes and proposed treatments using Chinese medicine[J]. Chin J Integr Med, 2017, 23(6): 461-468.

正常血镁Gitelman综合征1例的临床表现及基因诊断分析

Clinical manifestation and gene diagnosis of Gitelman syndrome with normal blood magnesium in 1 case

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