Primary Cilia Elongation in Early-Onset Polycystic Kidney Disease with 2 Hypomorphic PKD1 Alleles: A Case Report

Recent studies have described several children with very-early-onset polycystic kidney disease (PKD) that mimicked autosomal recessive polycystic kidney disease due to two hypomorphic PKD1 gene variants. However, no reports have described pathological changes in the primary cilia in these cases. We analyzed primary cilia in the kidney tubules of an early elementary school child who had very-early-onset PKD and a history of large, echogenic kidneys in utero. There was no family history of autosomal dominant polycystic kidney disease. The patient developed kidney failure and received a living-donor kidney transplant from his father. Genetic analysis revealed compound heterozygous variants in the PKD1 gene: c.3876C>A (p. Phe1292Leu) and c.5957C>T (p. Thr1986Met). These variants were likely pathogenic based on in silico analysis. The absence of kidney cysts in the parents suggested that these variants were hypomorphic alleles. Pathological examination of the patient's excised kidney showed prominent dilatation of the proximal and distal tubules. Immunofluorescence staining for α-tubulin showed pronounced elongation of the primary cilia. These findings suggest that the hypomorphic PKD1 variants expressed in this patient with very-early-onset PKD were pathogenic.