title: Recurrent ATP1A2 mutations in Portuguese families with familial hemiplegic migraine.
abstract: Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura. Three genes have been identified, all involved in ion transport. There is considerable clinical variation associated with FHM mutations. Genotype-phenotype correlation studies are needed, but are challenging mainly because the number of carriers of individual mutations is low. One exception is the recurrent T666M mutation in the FHM1 CACNA1A gene that was identified in almost one-third of FHM families and showed variable associated clinical features and severity, both within and among FHM families. Similar studies in the FHM2 ATP1A2 gene have not been performed because of the low number of carriers with individual mutations. Here we report on the recurrence of ATP1A2 mutations M731T and T376M that affect sodium-potassium pump functioning in two Portuguese FHM families. Considerably increasing the number of mutation carriers with these mutations indicated a clear genotype-phenotype correlation: both mutations are associated with pure FHM. In addition, we show that recurrent mutations for ATP1A2 are more frequent than previously thought, which has implications for genotype-phenotype correlations and genetic testing.
authors.affiliation: Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.|UnIGENe, IBMC - Instituto Biologia Molecular Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Castro
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anine H
authors.initials: AH
authors.lastname: Stam
authors.affiliation: Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.|UnIGENe, IBMC - Instituto Biologia Molecular Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Carolina
authors.initials: C
authors.lastname: Lemos
authors.affiliation: Serviço de Neurologia, Hospital Geral de Santo António (HGSA), Largo Abel Salazar, 4099-001, Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Barros
authors.affiliation: Instituto de Medicina Molecular (IMM), Lisbon Faculty of Medicine, Lisboa, Portugal.
authors.forename: Raquel G
authors.initials: RG
authors.lastname: Gouveia
authors.affiliation: Instituto de Medicina Molecular (IMM), Lisbon Faculty of Medicine, Lisboa, Portugal.
authors.forename: Isabel Pavão
authors.initials: IP
authors.lastname: Martins
authors.affiliation: Department of Pharmacology and Toxicology, Nijmegen, University Medical Centre St Radboud, Nijmegen, The Netherlands.
authors.forename: Jan B
authors.initials: JB
authors.lastname: Koenderink
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Kaate R J
authors.initials: KRJ
authors.lastname: Vanmolkot
authors.affiliation: Serviço de Neurologia, Centro Hospitalar do Nordeste, Mirandela, Portugal.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Mendes
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rune R
authors.initials: RR
authors.lastname: Frants
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.affiliation: Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.|UnIGENe, IBMC - Instituto Biologia Molecular Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sequeiros
authors.affiliation: Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal. permonteiro@mail.telepac.pt.|Serviço de Neurologia, Hospital Geral de Santo António (HGSA), Largo Abel Salazar, 4099-001, Porto, Portugal. permonteiro@mail.telepac.pt.
authors.forename: José M
authors.initials: JM
authors.lastname: Pereira-Monteiro
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.|Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arn M J M
authors.initials: AMJM
authors.lastname: van den Maagdenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000453:epidemiology / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011174:Portugal / Q000453:epidemiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
chemical_list: C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase