ATP1A2 mutations in 11 families with familial hemiplegic migraine

Familial hemiplegic migraine (FHM) is an autosomal dominant form of migraine with aura. The disease is caused by mutations of at least three genes among which two have been identified, CACNA1A and ATP1A2. Very few mutations have been identified so far in ATP1A2. We screened the coding sequence of ATP1A2 in 26 unrelated FHM probands in whom CACNA1A screening was negative. A total of eight different mutations were identified in 11 of the probands (41%), including six missense mutations, one small deletion leading to a frameshift, and one in frame deletion. All were novel mutations. Two mutations were recurrent, in three and two families, respectively. Genotyping of 94 relatives of these 11 probands identified 47 mutation carriers, among whom 36 were clinically affected. Sequencing of all 23 exons in an ethnically matched panel detected only one exonic coding polymorphism. © 2005 Wiley‐Liss, Inc.

[1]  A. Palotie,et al.  Kinetic Alterations due to a Missense Mutation in the Na,K-ATPase α2 Subunit Cause Familial Hemiplegic Migraine Type 2* , 2004, Journal of Biological Chemistry.

[2]  M. Leppert,et al.  Alternating hemiplegia of childhood or familial hemiplegic migraine?: A novel ATP1A2 mutation , 2004, Annals of neurology.

[3]  M. Dichgans,et al.  Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase variants , 2004, Neurology.

[4]  A. Palotie,et al.  A novel missense ATP1A2 mutation in a Finnish family with familial hemiplegic migraine type 2 , 2004, Neurogenetics.

[5]  M. Ferrari,et al.  New discoveries about the second gene for familial hemiplegic migraine, ATP1A2 , 2003, The Lancet Neurology.

[6]  J. D. den Dunnen,et al.  Standardizing mutation nomenclature: Why bother? , 2003, Human mutation.

[7]  J. Hottenga,et al.  Novel mutations in the Na+, K+‐ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions , 2003, Annals of neurology.

[8]  A. Ballabio,et al.  Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2 , 2003, Nature Genetics.

[9]  Kathryn A. O’Donnell,et al.  An mRNA Surveillance Mechanism That Eliminates Transcripts Lacking Termination Codons , 2002, Science.

[10]  E. Vicaut,et al.  The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. , 2001, The New England journal of medicine.

[11]  S. Antonarakis,et al.  Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion , 2000 .

[12]  G. Blanco,et al.  Isozymes of the Na-K-ATPase: heterogeneity in structure, diversity in function. , 1998, American journal of physiology. Renal physiology.

[13]  A. Verier,et al.  Mapping of a second locus for familial hemiplegic migraine to 1q21–q23 and evidence of further heterogeneity , 1997, Annals of neurology.

[14]  M. Barmada,et al.  A new locus for hemiplegic migraine maps to chromosome 1q31 , 1997, Neurology.

[15]  Dennis E Bulman,et al.  Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4 , 1996, Cell.

[16]  G. Ponsot,et al.  Genetic heterogeneity of familial hemiplegic migraine. , 1994, American journal of human genetics.