Novel mutations in the Na⁺, K⁺‐ATPase pump gene <i>ATP1A2</i> associated with familial hemiplegic migraine and benign familial infantile convulsions

TLDR

Familial hemiplegic migraine is a rare, severe autosomal dominant migraine with aura, most often caused by CACNA1A mutations that can also lead to epilepsy. The study reports novel missense mutations in the ATP1A2 Na⁺/K⁺‑ATPase pump gene on chromosome 1q23 in two FHM families. The M731T mutation was found in a family with pure FHM, and the R689Q mutation in a family with both FHM and benign familial infantile convulsions; all affected members carried the ATP1A2 mutation, underscoring that FHM linked to 1q23 involves ion‑transport dysfunction and epilepsy.

Abstract

Abstract Familial hemiplegic migraine (FHM) is a rare, severe, autosomal dominant subtype of migraine with aura. Up to 75% of FHM families have a mutation in the P/Q‐type calcium channel Ca v 2.1 subunit CACNA1A gene on chromosome 19p13. Some CACNA1A mutations also may cause epilepsy. Here, we describe novel missense mutations in the ATP1A2 Na + ,K + ‐ATPase pump gene on chromosome 1q23 in two families with FHM. The M731T mutation was found in a family with pure FHM. The R689Q mutation was identified in a family in which FHM and benign familial infantile convulsions partially cosegregate. In this family, all available affected family members with FHM, benign familial infantile convulsions, or both, carry the ATP1A2 mutation. Like FHM linked to 19p13, FHM linked to 1q23 also involves dysfunction of ion transportation and epilepsy is part of its phenotypic spectrum.