Open AccessGitelman syndrome with a novel frameshift variant in SLC12A3 gene accompanied by chronic kidney disease and type 2 diabetes mellitus
Author(s) -
Kenichiro Iio,
Takayasu Mori,
Saki Bessho,
Yosuke Imai,
Masaki Hatanaka,
Hiroki Omori,
Haruhiko Kouhara,
Motoko Chiga,
Eisei Sohara,
Shinichi Uchida,
Jun-Ya Kaimori
Publication year - 2021
Publication title -
cen case reports
Language(s) - English
Resource type - Journals
ISSN - 2192-4449
DOI - 10.1007/s13730-021-00652-4
Subject(s) - medicine , hypocalciuria , gitelman syndrome , hypokalemia , hypomagnesemia , endocrinology , missense mutation , nephrology , type 2 diabetes mellitus , diabetes mellitus , kidney disease , sanger sequencing , renal function , gastroenterology , genetics , mutation , biology , gene , materials science , magnesium , metallurgy
Gitelman syndrome is an autosomal recessive genetic disease caused by pathogenic variants in SLC12A3 resulting in the loss of function of the Na-Cl co-transporter (NCC) in the distal tubules. Hypokalemia and diuretic effects can cause secondary type 2 diabetes and renal function decline. Here, we present the case of a 49-year-old male patient with chronic persistent treatment-resistant hypokalemia for the past 13 years who had been receiving treatment for type 2 diabetes mellitus for 6 years. He was referred to our department due to the presence of urinary protein, impaired renal function, high renin activity, and hyperaldosteronism. Laboratory test results showed hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Using next-generation and Sanger sequencing, we identified a novel stop-gain variant (NM_000339.3:c.137del [p.His47fs]) and a missense variant (NM_000339.3:c.2927C > T [p.Ser976Phe]) in the SLC12A3 gene. This novel pathogenic variant was located at the intracellular N-terminus of the NCC. Based on these findings, the patient was diagnosed with Gitelman syndrome. The use of next-generation sequencing facilitated the exclusion of diseases with similar clinical symptoms.