Gitelman syndrome (GS) is an autosomal recessive kidney disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. The disorder is named for Gitelman, an American nephrologist. He first described it in 1966, after observing a pair of sisters with the disorder. The disorder is caused by inactivating mutations in the SLC12A3 gene, resulting in improper function of the thiazide-sensitive sodium-chloride co-transporter located in the distal convoluted tubule of the kidney. GS was formerly considered a subset of Bartter syndrome until the distinct genetic and molecular bases of these disorders were identified. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. This review aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.
ObjectiveTo screen pathogenic gene mutations of Gitelman syndrome (GS).MethodsPatients with GS diagnosed and treated in the Department of Endocrinology and Metabolism, West China Hospital of Sichuan University from January 2015 to December 2020 and their family members were included. The pathogenic genes were screened by second-generation sequencing combined with first-generation validation.ResultsA total of 15 GS patients were included. Gene analysis of patients indicated SLC12A3 gene mutation, including 9 cases of compound heterozygous mutation and 6 cases of heterozygous mutation. A total of 12 reported pathogenic sites and 8 new pathogenic mutations were found. Among the newly discovered pathogenic mutations, four were missense mutations (c.539C>A, p.T180K; c.1077C>G, p.N359K; c.1967C>T, p.P656L; and c.2963T>C, p.I988T), one was frame shift mutation caused by single base deletion (c.2543delA, p.D848fs), one was nonsense mutation (c.2129C>A, p.S710X), one was large fragment deletion (exon 7-8 partial coding sequence deletion), and one was coding sequence deletion and abnormal base sequence insertion (IVS7-1 to c.976 deletion GCGGACATTTTTG insertion into ACCGAAAATTTT).ConclusionIn this study, 8 new gene mutations leading to GS were found, and the exact pathogenesis of GS remains to be further confirmed.