Disease-causing germline mutations in the ATP1A1 gene have been discovered for the first time in 2018 by Lassuthova (and Colleagues) and by Schlingmann (and Colleagues).
Lassuthova et al. found heterozygous ATP1A1 pathogenic variants in several individuals belonging to seven distinct families with a late-onset axonal Charcot-Marie-Tooth (CMT) peripheral neuropathy. This form is currently classified as CMT type 2DD (CMT2DD). In the same year, Schlingmann et al. discovered heterozygous ATP1A1 pathogenic variants in three unrelated children presenting with hypomagnesemia and intractable seizures associated with severe intellectual disability (HOMGSMR2).
After these initial descriptions, the ATP1A1-related disorders have been enlarged to include neurodevelopmental phenotype (i.e., developmental delay/intellectual disability), with or without epilepsy and with or without motor involvement in the form of spasticity and/or neuropathy.
Currently only 20 families have been described worldwide. The disease is inherited in an autosomal dominant fashion. With the exception of CMT2DD familial cases, other patients are isolated (i.e., sporadic) cases.
Finally, somatic mutations in ATP1A1 were found in aldosterone-producing adenomas.
ATP1A1