Supplementary Material for: Genotype/Phenotype Analysis in 67 Chinese Patients with Gitelman's Syndrome

Background: Gitelman's syndrome (GS) is an autosomal recessive renal tubular disorder, which is caused by the mutations in SLC12A3. This study was designed to analyze the characteristics of the genotype and phenotype, and follow-up in the largest group of Chinese patients with GS. Methods: Sixty-seven patients with GS underwent SLCl2A3 analysis, and their clinical characteristics and biochemical findings as well as follow-up were reviewed, aiming to achieve a better description of GS. Additionally, the association of genotype and phenotype was explored. Results: Forty-one different mutations were identified within these 67 GS patients, including 11 novel mutations and 5 recurrent ones. Typical hypocalciuria and hypomagnesemia were not found in 6 (9%) and 8 (11.9%) patients, respectively. Male patients and those harboring severe mutations in both alleles had significant higher urinary fractional excretion (FE) of potassium, magnesium and chlorine. In addition, there were 2 patients who had chronic kidney disease (estimated glomerular filtration rate 2) and 32 patients with abnormal glucose metabolism. Conclusions: We identified 41 mutations related to GS, containing 11 novel variants and 5 high-frequency ones, which should facilitate earlier and more accurate diagnosis of GS. FE of electrolytes in urine may be more sensitive in the phenotype evaluation and differential diagnosis than corresponding serum electrolytes. Hypokalemia and hypomagnesemia in GS were difficult to correct; however, spironolactone might be helpful for hypokalemia to some degree. Compared with normal people, patients with GS were at higher risk of developing type 2 diabetes.

背景：吉特曼综合征（Gitelman's syndrome, GS）是一种常染色体隐性遗传性肾小管疾病，由SLC12A3基因突变所致。本研究旨在针对目前中国规模最大的GS患者队列，分析其基因型与表型特征，并开展随访研究。
方法：本研究对67例确诊GS的患者进行SLC12A3基因检测，回顾性分析其临床特征、生化检测结果及随访资料，以期更全面地描述GS的疾病表型，并探讨基因型与表型之间的关联。
结果：本研究在67例GS患者中共检出41种不同的突变，其中包括11种新发突变与5种复发性突变。分别有6例（9.0%）和8例（11.9%）患者未出现典型的低钙尿症与低镁血症。男性患者及双等位基因均携带严重突变的患者，其尿液钾、镁、氯的排泄分数（urinary fractional excretion, FE）显著升高。此外，有2例患者合并慢性肾脏病（估算肾小球滤过率为2），32例患者存在糖代谢异常。
结论：本研究共检出41种与GS相关的突变，其中包含11种新发变异与5种高频突变，该结果有助于实现GS的早期精准诊断。尿液电解质排泄分数在表型评估与鉴别诊断中，或较对应血清电解质指标更为敏感。GS患者的低钾血症与低镁血症较难纠正，但螺内酯可在一定程度上改善低钾血症。与健康人群相比，GS患者罹患2型糖尿病的风险显著升高。