The Importance of Molecular Testing in the Diagnosis of Genetic Syndromes with Chronic Kidney Disease: Genotype–Phenotype Correlations

Globally, chronic kidney disease (CKD) affects over 800 million individuals and is characterized by significant genetic complexity. More than 600 genes are associated with hereditary kidney disease, which may manifest as isolated kidney issues or as part of a syndrome that also includes extrarenal manifestations. The aim of this study was to identify genetic variants in a group of ten patients who presented with clinical signs suggestive of genetic syndromes associated with CKD, or who were asymptomatic but had a positive family history of CKD. Extensive genetic testing (targeted gene panels and whole-exome sequencing-WES) identified a mutation in the <i>PKD1</i> gene in 3 out of 10 cases. In one patient, a known mutation in the <i>PKD2</i> gene was identified. Another four patients were diagnosed with Alport syndrome: three of these presented with de novo missense mutations in the <i>COL4A5</i> gene, and one patient had a mutation in the <i>COL4A3</i> gene. One patient was diagnosed with MODY5, caused by a known mutation in the <i>HNF1B</i> gene, and one patient was diagnosed with Bartter syndrome type 1, resulting from a known mutation in the <i>SLC12A1</i> gene. We present genotype-phenotype correlations, highlighting the particularities of each patient within their family context. Our findings emphasize the importance of genotype-phenotype correlations in refining diagnosis, personalizing therapeutic management, and providing essential genetic counseling for at-risk relatives.