In affected members of a family with familial hemiplegic migraine-2 (FHM2; 602481), previously reported by Terwindt et al. (1997), Vanmolkot et al. (2003) identified a 2170G-A transition in exon 15 of the ATP1A2 gene, resulting in an arg689-to-gln (R689Q) substitution. Three individuals with the mutation and FHM also had benign familial infantile convulsions (BFIC), 1 member had the mutation and only BFIC, and 2 members had the mutation and only migraine with or without aura. Pelzer et al. (2014) found that 4 affected members of the family reported by Vanmolkot et al. (2003) who had BFIC carried a heterozygous truncating mutation in the PRRT2 gene (614386.0016), consistent with benign familial infantile convulsions-2 (BFIC2; 605751). Thus, 2 different neurologic disorders segregated in this family; the diagnosis was more complex as both disorders showed incomplete penetrance.
Segall et al. (2005) found that the mutant R689Q and M731T (182340.0003) rat Atp1a2 proteins transfected into HeLa cells showed reduced catalytic turnover and increased apparent affinity for extracellular potassium. Segall et al. (2005) suggested that the disease phenotype is caused by decreased activity of the Na+/K+ pump, resulting in delayed extracellular potassium clearance and/or altered localized calcium handling or signaling.
