Comprehensive Exonic Sequencing of Hemiplegic Migraine-Related Genes in a Cohort of Suspected Probands Identifies Known and Potential Pathogenic Variants

Autor:	Neven Maksemous, Omar Ibrahim, Rod A. Lea, Cassie L. Albury, Larisa M. Haupt, Bronwyn Jenkins, Benjamin Tsang, Heidi G. Sutherland, Lyn R. Griffiths, Robert A. Smith
Rok vydání:	2020
Předmět:	Proband Migraine Disorders Hemiplegia Nerve Tissue Proteins Biology Article whole exome sequencing Cohort Studies ATP1A2 Exome Sequencing medicine Prevalence Missense mutation Humans familial hemiplegic migraine migraine lcsh:QH301-705.5 ion channel genes Familial hemiplegic migraine Exome sequencing Genetic testing Genetics variants medicine.diagnostic_test Base Sequence Membrane Proteins General Medicine Exons Sequence Analysis DNA medicine.disease mutations PNKD lcsh:Biology (General) Mutation PRRT2 paroxysmal movement disorders
Zdroj:	Cells Cells, Vol 9, Iss 2368, p 2368 (2020) Volume 9 Issue 11
ISSN:	2073-4409
Popis:	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&mdash CACNA1A, ATP1A2, and SCN1A&mdash 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, < 20% of HM cases referred for genetic testing have mutations in these genes and other genes with roles in ion and solute transport, and neurotransmission has also been implicated in some HM cases. In this study, we performed whole exome sequencing for 187 suspected HM probands referred for genetic testing, but found to be negative for 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f7547e8fa8927ea6b4390606fbe31f0 https://pubmed.ncbi.nlm.nih.gov/33126486 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.