Background: Ciliary dysfunction is increasingly recognized as a genetic basis of cystic kidney diseases. Although homozygous TTC21B mutations are classically associated with nephronophthisis type 12, emerging evidence suggests that heterozygous variants may also produce clinical phenotypes. We report a case of PKD-like cystic nephropathy with hypersplenism associated with a heterozygous TTC21B mutation.
Case Report: A 51-year-old man was evaluated for thrombocytopenia and renal dysfunction detected during routine testing. Magnetic resonance imaging revealed enlarged kidneys with numerous cysts. Bone marrow biopsy findings were consistent with secondary hypersplenism. Genetic analysis identified a heterozygous TTC21B frameshift variant (c.125dupA; p.Tyr42fs*), while no pathogenic variants were detected in PKD1, PKD2, or GANAB.
Conclusion: Heterozygous TTC21B variants may be associated with adult-onset PKD-like nephropathy with systemic features, potentially expanding the phenotypic spectrum of TTC21B-related ciliopathies.