[Genetic analysis of two patients with Gitelman syndrome]

Area of Science:

• Genetics and Molecular Biology
• Nephrology
• Rare Diseases

Background:

• Gitelman syndrome (GS) is a rare autosomal recessive disorder characterized by renal salt wasting.
• The genetic basis of GS is primarily associated with mutations in the SLC12A3 gene, encoding the thiazide-sensitive sodium-chloride cotransporter.
• Accurate genetic diagnosis is crucial for understanding disease mechanisms and patient management.

Observation:

• Two patients presented with clinical manifestations consistent with Gitelman syndrome, including electrolyte imbalances.
• Whole exome sequencing (WES) was performed on peripheral blood samples.
• Electrolyte levels were analyzed, and candidate variants were confirmed via Sanger sequencing.

Findings:

• Patient 1, a 27-year-old female, harbored compound heterozygous variants (c.1456G>A and c.179C>T) in the SLC12A3 gene.
• Patient 2, a 4-year-old male, presented with compound heterozygous variants (c.602-16G>A and c.805_806insTTGGCGTGGTCTCGGTCA) in the SLC12A3 gene.
• Both identified variants were predicted to be pathogenic according to ACMG guidelines.

Implications:

• The identified SLC12A3 gene variants are likely the underlying cause of Gitelman syndrome in these patients.
• This study expands the spectrum of known pathogenic variants associated with Gitelman syndrome.
• Genetic characterization aids in precise diagnosis and potential therapeutic strategies for Gitelman syndrome.