It is worth noting that 36 individuals with undiagnosed ataxia harbored at least two putative pathogenetic mutations in DEP-encoding genes and that nine of these share the same combination of multiple mutated genes (EPHA3/EPHB2, EPHB2/SRC, EPHA3/MPO, APOE/PIK3CA), encoding proteins that are mostly part of the Synaptogenesis Signaling Pathway. Here, PIK3CA is linked to cerebellar ataxia.