Unravelling the Genetic Landscape of Hemiplegic Migraine: Exploring Innovative Strategies and Emerging Approaches

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2024 Apr 27

PMID 38674378

Authors

Mohammed M Alfayyadh

Neven Maksemous

Heidi G Sutherland

Rod A Lea

Lyn R Griffiths

Affiliations

Soon will be listed here.

Abstract

Migraine is a severe, debilitating neurovascular disorder. Hemiplegic migraine (HM) is a rare and debilitating neurological condition with a strong genetic basis. Sequencing technologies have improved the diagnosis and our understanding of the molecular pathophysiology of HM. Linkage analysis and sequencing studies in HM families have identified pathogenic variants in ion channels and related genes, including , , and , that cause HM. However, approximately 75% of HM patients are negative for these mutations, indicating there are other genes involved in disease causation. In this review, we explored our current understanding of the genetics of HM. The evidence presented herein summarises the current knowledge of the genetics of HM, which can be expanded further to explain the remaining heritability of this debilitating condition. Innovative bioinformatics and computational strategies to cover the entire genetic spectrum of HM are also discussed in this review.

References

Lakich D, Kazazian Jr H, Antonarakis S, Gitschier J . Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nat Genet. 1993; 5(3):236-41. DOI: 10.1038/ng1193-236. View

Lee J, Parkes M . Genome-wide association studies and Crohn's disease. Brief Funct Genomics. 2011; 10(2):71-6. DOI: 10.1093/bfgp/elr009. View

Ferrari M, Goadsby P, Burstein R, Kurth T, Ayata C, Charles A . Migraine. Nat Rev Dis Primers. 2022; 8(1):2. DOI: 10.1038/s41572-021-00328-4. View

Onsongo G, Baughn L, Bower M, Henzler C, Schomaker M, Silverstein K . CNV-RF Is a Random Forest-Based Copy Number Variation Detection Method Using Next-Generation Sequencing. J Mol Diagn. 2016; 18(6):872-881. DOI: 10.1016/j.jmoldx.2016.07.001. View

. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018; 38(1):1-211. DOI: 10.1177/0333102417738202. View

Meng H, Xu H, Yu L, Lin G, He N, Su T . The SCN1A mutation database: updating information and analysis of the relationships among genotype, functional alteration, and phenotype. Hum Mutat. 2015; 36(6):573-80. DOI: 10.1002/humu.22782. View

Steiner T, Stovner L, Vos T . GBD 2015: migraine is the third cause of disability in under 50s. J Headache Pain. 2016; 17(1):104. PMC: 5108738. DOI: 10.1186/s10194-016-0699-5. View

Kruppa J, Ziegler A, Konig I . Risk estimation and risk prediction using machine-learning methods. Hum Genet. 2012; 131(10):1639-54. PMC: 3432206. DOI: 10.1007/s00439-012-1194-y. View

Pelzer N, de Vries B, Kamphorst J, Vijfhuizen L, Ferrari M, Haan J . PRRT2 and hemiplegic migraine: a complex association. Neurology. 2014; 83(3):288-90. DOI: 10.1212/WNL.0000000000000590. View

10.

Le Fort D, Safran A, Picard F, Bouchardy I, Morris M . Elicited repetitive daily blindness: a new familial disorder related to migraine and epilepsy. Neurology. 2004; 63(2):348-50. DOI: 10.1212/01.wnl.0000130251.59422.b4. View

11.

Kors E, Haan J, Giffin N, Pazdera L, Schnittger C, Lennox G . Expanding the phenotypic spectrum of the CACNA1A gene T666M mutation: a description of 5 families with familial hemiplegic migraine. Arch Neurol. 2003; 60(5):684-8. DOI: 10.1001/archneur.60.5.684. View

12.

Riant F, De Fusco M, Aridon P, Ducros A, Ploton C, Marchelli F . ATP1A2 mutations in 11 families with familial hemiplegic migraine. Hum Mutat. 2005; 26(3):281. DOI: 10.1002/humu.9361. View

13.

Eikermann-Haerter K, Baum M, Ferrari M, van den Maagdenberg A, Moskowitz M, Ayata C . Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice. Ann Neurol. 2009; 66(4):564-8. PMC: 2783310. DOI: 10.1002/ana.21779. View

14.

Dilekoz E, Houben T, Eikermann-Haerter K, Balkaya M, Lenselink A, Whalen M . Migraine mutations impair hippocampal learning despite enhanced long-term potentiation. J Neurosci. 2015; 35(8):3397-402. PMC: 4339352. DOI: 10.1523/JNEUROSCI.2630-14.2015. View

15.

Li B, Leal S . Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am J Hum Genet. 2008; 83(3):311-21. PMC: 2842185. DOI: 10.1016/j.ajhg.2008.06.024. View

16.

Schork N, Murray S, Frazer K, Topol E . Common vs. rare allele hypotheses for complex diseases. Curr Opin Genet Dev. 2009; 19(3):212-9. PMC: 2914559. DOI: 10.1016/j.gde.2009.04.010. View

17.

Lehner B . Molecular mechanisms of epistasis within and between genes. Trends Genet. 2011; 27(8):323-31. DOI: 10.1016/j.tig.2011.05.007. View

18.

Moore J, Asselbergs F, Williams S . Bioinformatics challenges for genome-wide association studies. Bioinformatics. 2010; 26(4):445-55. PMC: 2820680. DOI: 10.1093/bioinformatics/btp713. View

19.

Rice A, McLysaght A . Dosage-sensitive genes in evolution and disease. BMC Biol. 2017; 15(1):78. PMC: 5580218. DOI: 10.1186/s12915-017-0418-y. View

20.

De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L . Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet. 2003; 33(2):192-6. DOI: 10.1038/ng1081. View