Hemiplegic migraine type 2 caused by a novel variant within the P-type ATPase motif in ATP1A2 concomitant with a CACNA1A variant

Tomoya Kubota; Shin Nabatame; Ruka Sato; Manami Hama; Ujiakira Nishiike; Hideki Mochizuki; Masanori P Takahashi; Takao Takeshima

doi:10.1016/j.braindev.2021.05.011

Hemiplegic migraine type 2 caused by a novel variant within the P-type ATPase motif in ATP1A2 concomitant with a CACNA1A variant

Brain Dev. 2021 Oct;43(9):952-957. doi: 10.1016/j.braindev.2021.05.011. Epub 2021 Jun 3.

Authors

Tomoya Kubota¹, Shin Nabatame², Ruka Sato³, Manami Hama³, Ujiakira Nishiike⁴, Hideki Mochizuki⁴, Masanori P Takahashi⁵, Takao Takeshima⁶

Affiliations

¹ Department 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.
² Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 5650871, Japan.
³ Department of Clinical Laboratory and Biomedical Sciences, Division of Health Sciences, Osaka University Graduate School of Medicine, 1-7, Yamadaoka, Suita, Osaka 5650871, Japan.
⁴ Department of Neurology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 5650871, Japan.
⁵ Department 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. Electronic address: mtakahas@sahs.med.osaka-u.ac.jp.
⁶ Department of Neurology, Tominaga Hospital, 1-4-48, Minato-cho, Naniwa-ku, Osaka, Osaka 5560017, Japan. Electronic address: ttakeshi@tominaga.or.jp.

PMID: 34092402
DOI: 10.1016/j.braindev.2021.05.011

Abstract

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.

Keywords: Case report; EEG; MRI-ASL; Na(+)/K(+)-ATPase; Voltage gated calcium channel.

Publication types

Case Reports

MeSH terms

Amino Acid Motifs
Calcium Channels / genetics*
Female
Genetic Testing
Humans
Middle Aged
Migraine with Aura / diagnosis
Migraine with Aura / genetics
P-type ATPases / chemistry
Pedigree
Sodium-Potassium-Exchanging ATPase / chemistry
Sodium-Potassium-Exchanging ATPase / genetics*

Substances

CACNA1A protein, human
Calcium Channels
ATP1A2 protein, human
P-type ATPases
Sodium-Potassium-Exchanging ATPase