Wang Fen, Shi Chuan, Cui Yunying, Li Chunyan, Tong Anli
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
Clin Exp Nephrol. 2017 Apr;21(2):293-299. doi: 10.1007/s10157-016-1284-6. Epub 2016 May 23.
Gitelman syndrome (GS) is a rare autosomal recessive disease caused by loss-of-function mutations in the SLC12A3 gene, and is characterized by hypokalemia and metabolic alkalosis. In this study, we aimed to study the genotype, phenotype, and treatment in 42 GS patients, the largest sample size so far in mainland China.
We retrospectively studied the clinical data and genetic characteristics of 42 patients diagnosed with GS in Peking Union Medical College Hospital from 2012 to 2015. Therapeutic efficacy of spironolactone and potassium supplements was also studied retrospectively.
Eighty-one mutation alleles were found in 42 patients, and total of 52 distinctly different mutation alleles were identified, of which 15 were new mutation alleles. p.Asp486Asn was a hotspot in our series, with the allele frequency being 19.7 % (16/81), and was found in 13 patients (31.0 %). Treatment with spironolactone or potassium supplements alone significantly increased serum potassium concentration by 0.36 ± 0.37 and 0.45 ± 0.35 mmol/l, respectively (both P < 0.05), and combined therapy with spironolactone and potassium increased serum potassium concentration by 0.69 ± 0.64 mmol/l (P < 0.05).
18.5 % (15/81) mutation sites identified in 42 Chinese GS patients are novel. p.Asp486Asn mutation is a hotspot, which is different from the reports from other countries. Spironolactone could moderately elevate serum potassium level, and spironolactone in combination with potassium supplements tended to be more effective.
吉特林综合征（GS）是一种由SLC12A3基因功能丧失性突变引起的罕见常染色体隐性疾病，其特征为低钾血症和代谢性碱中毒。在本研究中，我们旨在研究42例GS患者的基因型、表型及治疗情况，这是迄今为止中国大陆最大的样本量。
我们回顾性研究了2012年至2015年在北京协和医院确诊为GS的42例患者的临床资料和基因特征。同时也回顾性研究了螺内酯和补钾的治疗效果。
在42例患者中发现了81个突变等位基因，共鉴定出52个明显不同的突变等位基因，其中15个为新的突变等位基因。p.Asp486Asn是我们研究系列中的一个热点突变，等位基因频率为19.7%（16/81），在13例患者（31.0%）中被发现。单独使用螺内酯或补钾治疗可使血清钾浓度分别显著升高0.36±0.37和0.45±0.35 mmol/L（均P<0.05），螺内酯与补钾联合治疗可使血清钾浓度升高0.69±0.64 mmol/L（P<0.05）。
42例中国GS患者中鉴定出的18.5%（15/81）的突变位点是新的。p.Asp486Asn突变是一个热点突变，与其他国家的报道不同。螺内酯可适度提高血清钾水平，螺内酯与补钾联合使用往往更有效。
