The contribution of CACNA1A, ATP1A2 and SCN1A mutations in hemiplegic migraine : A clinical and genetic study in Finnish migraine families
| Autor: | Aarno Palotie, Petra Keski-Säntti, Maija Wessman, Mari A. Kaunisto, Matti Ilmavirta, Marja-Liisa Sumelahti, Salli Vepsäläinen, Marjo Eveliina Hiekkala, Paavo Häppölä, Eija Hämäläinen, Markus Färkkilä, Elisa Häppölä, Dennis Lal, E. Cuenca-Leon, Erkki Säkö, Hannele Havanka, Mikko Kallela, Padhraig Gormley, Ville Artto, Markku Nissilä, Pietari Vuola, Hanna Harno |
|---|---|
| Přispěvatelé: | Neurologian yksikkö, Clinicum, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Department of Neurosciences, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, HUS Neurocenter, Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Aura PROTEINS FEBRILE SEIZURES PLUS GENERALIZED EPILEPSY VARIANTS 3124 Neurology and psychiatry 03 medical and health sciences TYPE-2 0302 clinical medicine pathogenic variant CHANNEL ATP1A2 Internal medicine medicine Humans Generalized epilepsy ICHD-3 beta criteria clinical characteristics Exome sequencing Finland SPECTRUM CONSEQUENCES Genetic heterogeneity business.industry 3112 Neurosciences General Medicine Middle Aged medicine.disease Migraine with aura 3. Good health NAV1.1 Voltage-Gated Sodium Channel 030104 developmental biology Migraine Mutation ion channel International Classification of Headache Disorders Female Neurology (clinical) Calcium Channels medicine.symptom Sodium-Potassium-Exchanging ATPase business exome sequencing 030217 neurology & neurosurgery |
| Popis: | Objective To study the position of hemiplegic migraine in the clinical spectrum of migraine with aura and to reveal the importance of CACNA1A, ATP1A2 and SCN1A in the development of hemiplegic migraine in Finnish migraine families. Methods The International Classification of Headache Disorders 3rd edition criteria were used to determine clinical characteristics and occurrence of hemiplegic migraine, based on detailed questionnaires, in a Finnish migraine family collection consisting of 9087 subjects. Involvement of CACNA1A, ATP1A2 and SCN1A was studied using whole exome sequencing data from 293 patients with hemiplegic migraine. Results Overall, hemiplegic migraine patients reported clinically more severe headache and aura episodes than non-hemiplegic migraine with aura patients. We identified two mutations, c.1816G>A (p.Ala606Thr) and c.1148G>A (p.Arg383His), in ATP1A2 and one mutation, c.1994C>T (p.Thr665Met) in CACNA1A. Conclusions The results highlight hemiplegic migraine as a clinically and genetically heterogeneous disease. Hemiplegic migraine patients do not form a clearly separate group with distinct symptoms, but rather have an extreme phenotype in the migraine with aura continuum. We have shown that mutations in CACNA1A, ATP1A2 and SCN1A are not the major cause of the disease in Finnish hemiplegic migraine patients, suggesting that there are additional genetic factors contributing to the phenotype. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|