Analysis of two pedigrees of Gitelman syndrome complicated with proteinuria or Hashimoto's thyroiditis caused by SLC12A3 compound heterozygous mutation and literature review

Abstract

Gitelman syndrome (GS, OMIM263800) is a salt-losing renal tubular disease of autosomal recessive inheritance. The cause of GS is a functional deletion mutation of SLC12A3 encoding thiazide-sensitive NaCl cotransporter (NCCT) located in the distal convoluted tubules (DCT) of the kidney, which leads to dysfunction of sodium chloride reabsorption by the DCT, resulting in a series of pathophysiological changes and clinical manifestations such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. The disease has a high degree of phenotypic and genetic heterogeneity, and a clear relationship between genotype and phenotype remains to be established. Long-term chronic disorders relating to serum potassium and magnesium will lead to abnormal glucose metabolism and impaired renal function. In severe cases, serious clinical symptoms such as cartilage calcification, hand and foot convulsion, rhabdomyolysis, epilepsy, and ventricular arrhythmia can also occur. In this study, genetic linkage analysis was performed on two GS families with proteinuria or Hashimoto’s thyroiditis. The mutation location of the SLC12A3 gene was analyzed, and the phenotypic heterogeneity of GS and the relationship between genotype and phenotype were explored.

Date
Oct 4, 2020 12:00 AM
Event