Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase variants

• Published in: Neurology Vol. 62; no. 10; p. 1857
• Main Authors: Jurkat-Rott, K, Freilinger, T, Dreier, J P, Herzog, J, Göbel, H, Petzold, G C, Montagna, P, Gasser, T, Lehmann-Horn, F, Dichgans, M
• Format: Journal Article
• Language: English
• Published: United States 25.05.2004
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Amino Acid Substitution; Coma - genetics; DNA Mutational Analysis; Epilepsy - genetics; Female; Genetic Predisposition to Disease; Genotype; Hemiplegia - enzymology; Hemiplegia - genetics; Humans; Intellectual Disability - genetics; Male; Middle Aged; Migraine Disorders - enzymology; Migraine Disorders - genetics; Models, Molecular; Molecular Sequence Data; Mutation, Missense; Penetrance; Phenotype; Point Mutation; Recurrence; Sequence Alignment; Sequence Homology, Amino Acid; Sodium-Potassium-Exchanging ATPase - chemistry; Sodium-Potassium-Exchanging ATPase - genetics; Sodium-Potassium-Exchanging ATPase - physiology
• ISSN: 1526-632X
• DOI: 10.1212/01.WNL.0000127310.11526.FD

A1A2 Na+/K+-ATPase mutations cause familial hemiplegic migraine type 2 (FHM2). The authors identified three putative A1A2 mutations (D718N, R763H, P979L) and three that await validation (P796R, E902K, X1021R). Ten to 20% of FHM cases may be FHM2. A1A2 mutations have a penetrance of about 87%. D718N causes frequent, long-lasting HM, and P979L may cause recurrent coma. D718N and P979L may predispose to seizures and mental retardation. A1A2 does not play a major role in sporadic HM; only one variant, R383H, occurred in 1 of 24 cases.