Renal Agenesis in Kallmann Syndrome: A Network Approach

Summary Kallmann syndrome (KS) is defined by the combination of isolated hypogonadotrophic hypogonadism (IHH) and anosmia, with renal agenesis occurring in 30% of KS cases with KAL1 gene mutations. Unlike other KS‐related disorders, renal agenesis cannot be directly associated with mutations in the KAL1 gene. We hypothesized that protein interaction networks may suggest a link between genes currently known to be associated with KS on the one hand and those associated with renal agenesis on the other hand. We created a STRING protein interaction network from KS‐related genes and renal‐agenesis‐associated genes and analyzed it with Cytoscape 3.0.1 network software. The STRING protein interaction network provided a conceptual framework for current knowledge on the subject of renal morphogenesis in Kallmann syndrome. In addition, STRING and Cytoscape 3.0.1 software identified new potential KS renal‐aplasia‐associated genes (PAX2, BMP4, and SOX10). The use of protein–protein interaction networks and network analysis tools provided interesting insights and possible directions for future studies on the subject of renal aplasia in Kallmann syndrome.