The contribution of CACNA1A, ATP1A2 and SCN1A mutations in hemiplegic migraine: A clinical and genetic study in Finnish migraine families-Reference-Cited by-同舟云学术

The contribution of CACNA1A, ATP1A2 and SCN1A mutations in hemiplegic migraine: A clinical and genetic study in Finnish migraine families

Published:2018-02-27 Issue:12 Volume:38 Page:1849-1863
ISSN:0333-1024
Container-title:Cephalalgia
language:en
Short-container-title:Cephalalgia

Author:

Hiekkala Marjo Eveliina¹,Vuola Pietari¹²,Artto Ville²,Häppölä Paavo³,Häppölä Elisa¹,Vepsäläinen Salli²,Cuenca-León Ester⁴⁵,Lal Dennis⁵⁶⁷⁸,Gormley Padhraig⁵⁶⁹¹⁰,Hämäläinen Eija³,Ilmavirta Matti¹¹,Nissilä Markku¹²,Säkö Erkki¹³,Sumelahti Marja-Liisa¹⁴,Harno Hanna¹⁵,Havanka Hannele¹⁶,Keski-Säntti Petra¹⁷,Färkkilä Markus²,Palotie Aarno³⁴⁵⁶⁷,Wessman Maija¹³,Kaunisto Mari Anneli³,Kallela Mikko²

Affiliation:

1. Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland

2. Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland

3. Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland

4. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK

5. Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, USA

6. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA

7. Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA

8. Cologne Center for Genomics, University of Cologne, Cologne, Germany

9. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA

10. Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA

11. Department of Neurology, Central Hospital Central Finland, Jyväskylä, Finland

12. Terveystalo Clinical Research, Turku, Finland

13. Turku Headache Center, Turku, Finland

14. Terveystalo, Tampere, Finland

15. Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

16. Regional State Administrative Agency for Northern Finland, Oulu, Finland

17. Terveystalo, Helsinki, Finland

Abstract

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.

Funder

Wellcome Trust

Helsingin ja Uudenmaan Sairaanhoitopiiri

Sigrid Juséliuksen Säätiö

ENGAGE Consortium

EuroHead project

FP7-EUROHEADPAIN

Samfundet Folkhälsan

Academy of Finland Center of Excellence for Complex Disease Genetics

Medicinska Understödsföreningen Liv och Hälsa

Suomen Akatemia

Beatriu de Pinós AGAUR, Generalitat de Catalunya