Abstract:
Background Gitelman syndrome (GS) is the most frequent inherited tubulopathy, with atypical clinical manifestations and great risk of missed diagnosis and misdiagnosis. We have a late understanding of GS and the field of genetic research is relatively weak. There are few large sample studies on the genotype-phenotype correlations of GS patients in China.
Objective To investigate the clinical and genetic characteristics of GS, and improve the understanding, diagnosis and treatment of this disease.
Methods Clinical data about 71 patients with diagnosed GS in the Department of Endocrinology of the First Medical Centre of Chinese PLA General Hospital from July 2007 to September 2020 were collected, and genetic analysis was conducted, then the correlation between genotype and phenotype was explored.
Results Among the 71 GS patients, 44 cases were male and 27 cases were female, and the neuromuscular system was most frequently involved in the clinical manifestations. Female patients were more likely to develop muscle cramps (40.7% vs 18.2%, P=0.037) and limb numbness (37.0% vs 15.9%, P=0.043). All patients presented with hypokalemia at admission, while hypomagnesemia and typical hypocalciuria were not found in 16 (22.5%) and 6 (8.4%) patients, respectively. SLC12A3 gene mutations were not detected in 3 patients, and multiple gene deletions were suspected in 1 patient, and 70 different SLC12A3 gene mutation types were detected in the remaining 67 patients, of which 25 were new mutations. p.D486N and p.T60M were the most common mutations, which were found in 20 (28%) and 8 (11%) patients, respectively. The serum potassium level of homozygous mutation patients was significantly lower than that of compound heterozygous mutation patients (P=0.015).
Conclusion The genotype and phenotype of GS patients are obviously heterogeneous. Some patients have normal serum magnesium and urinary calcium levels. p.D486N and p.T60M are the hotspot mutations in this study. In addition to the SLC12A3 gene, there are other genetic factors that play roles in the pathological process of GS. Hypokalemia is relatively severe in patients with homozygous mutations.
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