UMOD Gene Mutations in Autosomal Dominant Tubulointerstitial Kidney Disease: First Cases Reported from Türkiye

Background: Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is a rare hereditary disorder that typically presents with slowly progressive chronic kidney disease (CKD), bland urinary sediment, hyperuricemia, and early-onset gout. Mutations in the UMOD gene are the most common cause. However, clinical heterogeneity remains underappreciated, particularly in underrepresented populations. Methods: We investigated three unrelated families from the same village in Türkiye with a history of CKD of unknown etiology. A total of 56 individuals were screened using Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) to identify pathogenic variants in UMOD , MUC1 , HNF1B , REN , and SEC61A1 genes. Results: A heterozygous missense variant in the UMOD gene (c.172G>A; p.Gly58Cys) was detected in 32 individuals. Among them, 14 had clinically confirmed CKD (mean age 60.9 years), and 18 were asymptomatic carriers (mean age 41.6 years). Notably, none of the affected individuals exhibited hyperuricemia or gout. This highlights considerable intrafamilial phenotypic variability and suggests that classical features may be absent even in genetically confirmed cases. Conclusion: To our knowledge, this is the first report of genetically confirmed ADTKD-UMOD cases from Türkiye. Our findings underscore the diagnostic value of genetic testing in familial CKD and demonstrate that UMOD -associated disease can manifest without hyperuricemia or gout. Increased awareness and early genetic screening are essential for accurate diagnosis and appropriate family counseling.