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Migraine Disorders: HELP
Articles by Dennis Lal
Based on 3 articles published since 2010
(Why 3 articles?)
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Between 2010 and 2020, Dennis Lal wrote the following 3 articles about Migraine Disorders.
 
+ Citations + Abstracts
1 Review SCN1A variants from bench to bedside-improved clinical prediction from functional characterization. 2019

Brunklaus, Andreas / Schorge, Stephanie / Smith, Alexander D / Ghanty, Ismael / Stewart, Kirsty / Gardiner, Sarah / Du, Juanjiangmeng / Pérez-Palma, Eduardo / Symonds, Joseph D / Collier, Abby C / Lal, Dennis / Zuberi, Sameer M. ·The Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, UK. · School of Medicine, University of Glasgow, Glasgow, UK. · Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK. · School of Pharmacy, University College London, London, UK. · Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada. · West of Scotland Genetic Services, Level 2B, Laboratory Medicine, Queen Elizabeth University Hospital, Glasgow, UK. · Cologne Center for Genomics, University Hospital Cologne, University of Cologne, Cologne, Germany. · Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts. · Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts. · Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio. · Genomic Medicine Institute, Lerner Research Institute Cleveland Clinic, Cleveland, Ohio. ·Hum Mutat · Pubmed #31782251.

ABSTRACT: Variants in the SCN1A gene are associated with a wide range of disorders including genetic epilepsy with febrile seizures plus (GEFS+), familial hemiplegic migraine (FHM), and the severe childhood epilepsy Dravet syndrome (DS). Predicting disease outcomes based on variant type remains challenging. Despite thousands of SCN1A variants being reported, only a minority has been functionally assessed. We review the functional SCN1A work performed to date, critically appraise electrophysiological measurements, compare this to in silico predictions, and relate our findings to the clinical phenotype. Our results show, regardless of the underlying phenotype, that conventional in silico software correctly predicted benign from pathogenic variants in nearly 90%, however was unable to differentiate within the disease spectrum (DS vs. GEFS+ vs. FHM). In contrast, patch-clamp data from mammalian expression systems revealed functional differences among missense variants allowing discrimination between disease severities. Those presenting with milder phenotypes retained a degree of channel function measured as residual whole-cell current, whereas those without any whole-cell current were often associated with DS (p = .024). These findings demonstrate that electrophysiological data from mammalian expression systems can serve as useful disease biomarker when evaluating SCN1A variants, particularly in view of new and emerging treatment options in DS.

2 Article Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families. 2018

Gormley, Padhraig / Kurki, Mitja I / Hiekkala, Marjo Eveliina / Veerapen, Kumar / Häppölä, Paavo / Mitchell, Adele A / Lal, Dennis / Palta, Priit / Surakka, Ida / Kaunisto, Mari Anneli / Hämäläinen, Eija / Vepsäläinen, Salli / Havanka, Hannele / Harno, Hanna / Ilmavirta, Matti / Nissilä, Markku / Säkö, Erkki / Sumelahti, Marja-Liisa / Liukkonen, Jarmo / Sillanpää, Matti / Metsähonkala, Liisa / Koskinen, Seppo / Lehtimäki, Terho / Raitakari, Olli / Männikkö, Minna / Ran, Caroline / Belin, Andrea Carmine / Jousilahti, Pekka / Anttila, Verneri / Salomaa, Veikko / Artto, Ville / Färkkilä, Markus / Anonymous71040 / Anonymous81040 / Runz, Heiko / Daly, Mark J / Neale, Benjamin M / Ripatti, Samuli / Kallela, Mikko / Wessman, Maija / Palotie, Aarno. ·Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. · Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland. · Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. · Merck Research Laboratories, Merck and Co., Kenilworth, NJ, USA. · Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cologne Center for Genomics, University of Cologne, Cologne, Germany. · Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. · Regional State Administrative Agency for Northern Finland, Oulu, Finland. · Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland; Division of Pain Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Finland. · Department of Neurology, Central Hospital Central Finland, Jyväskylä. · Terveystalo Clinical Research, Turku, Finland. · Turku Headache Center, Turku, Finland. · Terveystalo, Tampere, Finland. · Lääkärikeskus Ikioma, Mikkeli, Finland. · Departments of Child Neurology and General Practice, University of Turku, and Turku University Hospital, Turku, Finland. · Epilepsy Unit for Children and Adolescents, Helsinki University Hospital, Helsinki, Finland. · National Institute for Health and Welfare, Helsinki, Finland. · Department of Clinical Chemistry, Fimlab Laboratories, Faculty of Medicine and Life Sciences, University of Tampere, Finland. · Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland. · Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland. · Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. · Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. · 23andMe, Inc., Mountain View, CA, USA. · Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland; Public Health, Faculty of Medicine, University of Helsinki, Finland. · Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. · Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. Electronic address: aarno.palotie@helsinki.fi. ·Neuron · Pubmed #29731251.

ABSTRACT: Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 × 10

3 Article The contribution of CACNA1A, ATP1A2 and SCN1A mutations in hemiplegic migraine: A clinical and genetic study in Finnish migraine families. 2018

Hiekkala, Marjo Eveliina / Vuola, Pietari / Artto, Ville / Häppölä, Paavo / Häppölä, Elisa / Vepsäläinen, Salli / Cuenca-León, Ester / Lal, Dennis / Gormley, Padhraig / Hämäläinen, Eija / Ilmavirta, Matti / Nissilä, Markku / Säkö, Erkki / Sumelahti, Marja-Liisa / Harno, Hanna / Havanka, Hannele / Keski-Säntti, Petra / Färkkilä, Markus / Palotie, Aarno / Wessman, Maija / Kaunisto, Mari Anneli / Kallela, Mikko. ·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. ·Cephalalgia · Pubmed #29486580.

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.