Targeted next-generation sequencing provides novel clues for associated epilepsy and cardiac conduction disorder/SUDEP

Antonio Oliva, Monica Coll Vidal, Bernard Del Olmo Cabestre', Monica Coll, Pasquale Striano, Carles Ferrer-Costa, Oscar Campuzano, Jesús Matés, Bernat Del Olmo, Anna Iglesias, Alexandra Pérez-Serra, Irene Mademont, Ferran Picó, Ramon Brugada

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

12 Citazioni (Scopus)

Abstract

Sudden unexpected death in epilepsy is an unpredicted condition in patients with a diagnosis of epilepsy, and autopsy does not conclusively identify cause of death. Although the pathophysiological mechanisms that underlie this entity remain unknown, the fact that epilepsy can affect cardiac function is not surprising. The genetic factors involving ion channels co-expressed in the heart and brain and other candidate genes have been previously described. In the present study, 20 epilepsy patients with personal or family history of heart rhythm disturbance/cardiac arrhythmias/sudden death were sequenced using a custom resequencing panel. Twenty-six relatives were genetically analysed to ascertain the family segregation in ten individuals. Four subjects revealed variants with positive genotype-phenotype segregation: four missense variants in the CDKL5, CNTNAP2, GRIN2A and ADGRV1 genes and one copy number variant in KCNQ1. The potential pathogenic role of variants in new candidate genes will need further studies in larger cohorts, and the evaluation of the potential pathogenic role in the cardio-cerebral mechanisms requires in vivo/in vitro studies. In addition to family segregation, evaluation of the potential pathogenic roles of these variants in cardio-cerebral mechanisms by in vivo/in vitro studies should also be performed. The potential pathogenic role of variants in new candidate genes will need further studies in larger cohorts.
Lingua originaleEnglish
pagine (da-a)e0189618-16
RivistaPLoS One
Volume12
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Adolescent
  • Adult
  • Agricultural and Biological Sciences (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Cardiac Conduction System Disease
  • Child
  • Chromosome Segregation
  • Cohort Studies
  • Death, Sudden
  • Epilepsy
  • Exons
  • Female
  • Genetic Variation
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Inheritance Patterns
  • Male
  • Middle Aged
  • Pedigree
  • Sequence Deletion
  • Young Adult

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