Genetic Characterization of Lithuanian Patients With Cystic Kidney

Cystic kidney diseases are genetically and clinically heterogeneous. Despite advances in genetic testing, some patients remain undiagnosed, limiting targeted care. This study explores the genetic causes in Lithuanian patients with multiple kidney cysts. Genetic testing using kidney-focused next-generation sequencing or Sanger sequencing was performed on 114 patients. Genetic and clinical data from individuals with detected variants were analyzed. Diagnostic variants were identified in 69% of families; variants of uncertain significance in 13%, and the remaining families were undiagnosed. The diagnostic yield was 73% in Group 1 (defined cystic kidney phenotype) and 61% in Group 2 (nonspecific kidney cysts). In total, 24 novel variants were identified in seven genes. Autosomal dominant polycystic kidney disease (ADPKD) was the most common diagnosis. Among patients with nonspecific cysts, variants were found in PKD1, COL4A5, HNF1B, NPHP1, PAX2, TSC2, and UMOD, while 39% remained genetically unresolved. Patients with non-ADPKD diagnoses typically showed multiple cysts without a definitive phenotype. Most patients harbored disease-causing variants, with novel variants that will contribute to the ADPKD Variant Database. While ciliopathies are frequently recognized, genetic glomerulopathies may also present with a cystic phenotype. Genetic testing should be considered in cases of nonspecific multiple kidney cysts.