eP291: Disease characterization in sodium-potassium ATPases by reverse genetics in humans

Most genetic disorders are discovered via forward genetics: a shared phenotype is recognized in a group of patients, allowing causative gene(s) to be determined. This can lead to excessively narrow definitions of disease phenotypes due to selection bias, as patients with symptoms outside the “classic” presentation are less likely to be diagnosed. We hypothesized that reverse human genetics, ie, studying variants in a gene without phenotype-based recruitment, could more accurately characterize new diseases.