Autosomal Dominant Polycystic Kidney Disease (ADPKD) and X-Linked Alport Syndrome (AS) are the most common monogenic causes of chronic kidney disease (CKD), each capable of independently leading to end-stage kidney disease (ESKD). However, the concurrent presence of both disorders in a single individual is exceedingly rare and poses significant diagnostic complexity. We report a unique case involving dual diagnosis of ADPKD and AS, attributed to a paternal PKD1 variant and a maternally inherited COL4A5 variant. Initial genetic testing through next-generation sequencing (NGS) identified PKD1 and COL4A5 variants in the Proband. While Sanger sequencing confirmed the PKD1 variant in the father, Sanger analysis of the Mother did not detect the COL4A5 variant despite her clinical signs, including persistent microhematuria and basement membrane abnormalities on electron microscopy. Further investigation using high-sensitivity approaches, like customised amplicon-based deep sequencing, confirmed low-level mosaicism for the COL4A5 variant in the Mother. This case underscores the critical role of advanced genetic testing in resolving atypical or dual presentations of kidney disease and highlights the need to consider mosaicism in unexplained inheritance patterns. Comprehensive family evaluation and precision diagnostics are essential for accurate counselling and management in such complex cases. This report contributes to the expanding spectrum of dual monogenic kidney disease.
Shanmugam et al. (Sun,) studied this question.