Comprehensive Exonic Sequencing of Hemiplegic Migraine-Related Genes in a Cohort of Suspected Probands Identifies Known and Potential Pathogenic Variants
Heidi G. Sutherland,
Neven Maksemous,
Cassie L. Albury,
Omar Ibrahim,
Robert A. Smith,
Rod A. Lea,
Larisa M. Haupt,
Bronwyn Jenkins,
Benjamin Tsang,
Lyn R. Griffiths
Affiliations
Heidi G. Sutherland
Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Neven Maksemous
Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Cassie L. Albury
Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Omar Ibrahim
Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Robert A. Smith
Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Rod A. Lea
Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Larisa M. Haupt
Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Bronwyn Jenkins
The Epping Clinic, Sydney, NSW 2121, Australia
Benjamin Tsang
Department of Neurology, Sunshine Coast University Hospital, Birtinya, QLD 4575, Australia
Lyn R. Griffiths
Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Hemiplegic migraine (HM) is a rare migraine disorder with aura subtype including temporary weakness and visual, sensory, and/or speech symptoms. To date, three main genes—CACNA1A, ATP1A2, and SCN1A—have been found to cause HM. These encode ion channels or transporters, important for regulating neuronal ion balance and synaptic transmission, leading to HM being described as a channelopathy. However, CACNA1A, ATP1A2, and SCN1A mutations, and applied targeted analysis of whole exome sequencing data for rare missense or potential protein-altering variants in the PRRT2, PNKD, SLC1A3, SLC2A1, SLC4A4, ATP1A3, and ATP1A4 genes. We identified known mutations and some potentially pathogenic variants in each of these genes in specific cases, suggesting that their screening improves molecular diagnosis for the disorder. However, the majority of HM patients were found not to have candidate mutations in any of the previously reported HM genes, suggesting that additional genetic factors contributing to the disorder are yet to be identified.
