A Novel ATP1A2 Gene Mutation in an Irish Familial Hemiplegic Migraine Kindred

Objective.— We studied a large Irish Caucasian pedigree with familial hemiplegic migraine (FHM) with the aim of finding the causative gene mutation. Background.— FHM is a rare autosomal‐dominant subtype of migraine with aura, which is linked to 4 loci on chromosomes 19p13, 1q23, 2q24, and 1q31. The...

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Bibliographic Details
Published in:Headache 2008-01, Vol.48 (1), p.101-108
Main Authors: Fernandez, Desiree M., Hand, Collette K., Sweeney, Brian J., Parfrey, Nollaig A.
Format: Article
Language:English
Subjects:
Aspartic Acid - genetics
ATP1A2 gene mutation
Biological and medical sciences
Calcium Channels - genetics
Cardiovascular system
Chromosome Mapping
Chromosomes, Human, Pair 1
DNA Mutational Analysis
Exons
familial hemiplegic migraine
Family Health
Female
Gene Frequency
Genetic Testing
Histidine - genetics
Humans
Ireland
Male
Medical sciences
Migraine with Aura - genetics
Mutation - genetics
NAV1.1 Voltage-Gated Sodium Channel
Nerve Tissue Proteins - genetics
Neurology
Pharmacology. Drug treatments
Sodium Channels - genetics
Sodium-Potassium-Exchanging ATPase - genetics
Vascular diseases and vascular malformations of the nervous system
Vasodilator agents. Cerebral vasodilators
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Summary:Objective.— We studied a large Irish Caucasian pedigree with familial hemiplegic migraine (FHM) with the aim of finding the causative gene mutation. Background.— FHM is a rare autosomal‐dominant subtype of migraine with aura, which is linked to 4 loci on chromosomes 19p13, 1q23, 2q24, and 1q31. The mutations responsible for hemiplegic migraine have been described in the CACNA1A gene (chromosome 19p13), ATP1A2 gene (chromosome 1q23), and SCN1A gene (chromosome 2q24). Methods.— We performed linkage analyses in this family for chromosome 1q23 and performed mutation analysis of the ATP1A2 gene. Results.— Linkage to the FHM2 locus on chromosome 1 was demonstrated. Mutation screening of the ATP1A2 gene revealed a G to C substitution in exon 22 resulting in a novel protein variant, D999H, which co‐segregates with FHM within this pedigree and is absent in 50 unaffected individuals. This residue is also highly conserved across species. Conclusions.— We propose that D999H is a novel FHM ATP1A2 mutation.
ISSN:0017-8748
1526-4610
DOI:10.1111/j.1526-4610.2007.00848.x