Hemiplegic migraine type 2 caused by a novel variant within the P-type ATPase motif in ATP1A2 concomitant with a
Tomoya Kubota1, Shin Nabatame2, Ruka Sato3
1Department of Clinical Laboratory and Biomedical Sciences, Division of Health Sciences, Osaka University Graduate School of Medicine, 1-7, Yamadaoka, Suita, Osaka 5650871, Japan; Department of Neurology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 5650871, Japan.
Background:
Familial hemiplegic migraine (FHM) is an inherited autosomal dominant disorder characterized by migraine with reversible hemiplegia. FHM1 is caused by variants in CACNA1A, encoding a P/Q type neuronal voltage-gated calcium channel α subunit, which is also associated with episodic ataxia type 2 (EA2). FHM2 is associated with ATP1A2, which codes for an Na+/K+-ATPase isoform 2 subunit.
Case Presentation:
We identified an FHM2 family, the mother and her daughter, with a novel variant in ATP1A2, p.Gly377Asp, located in a well-conserved P-type ATPase motif. Additionally, the mother harbored deletion in the CACNA1A, associated with EA2, but her daughter did not. The mother presented migraine with typical aura without motor deficit, whereas her daughter had migraine accompanied by recurrent motor deficit and altered consciousness. The additional CACNA1A deletion in the mother might serve as a modifier.
Conclusion:
Our report emphasizes the importance of genetic analysis to diagnose neurological ion channel/transporter diseases.
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