title: Identification of Genetic Alterations, as Causative Genetic Defects in Long QT Syndrome, Using Next Generation Sequencing Technology.
abstract: Long QT Syndrome is an inherited channelopathy leading to sudden cardiac death due to ventricular arrhythmias. Despite that several genes have been associated with the disease, nearly 20% of cases remain without an identified genetic cause. Other genetic alterations such as copy number variations have been recently related to Long QT Syndrome. Our aim was to take advantage of current genetic technologies in a family affected by Long QT Syndrome in order to identify the cause of the disease.
  
  
  
  Complete clinical evaluation was performed in all family members. In the index case, a Next Generation Sequencing custom-built panel, including 55 sudden cardiac death-related genes, was used both for detection of sequence and copy number variants. Next Generation Sequencing variants were confirmed by Sanger method. Copy number variations variants were confirmed by Multiplex Ligation dependent Probe Amplification method and at the mRNA level. Confirmed variants and copy number variations identified in the index case were also analyzed in relatives.
  
  
  
  In the index case, Next Generation Sequencing revealed a novel variant in TTN and a large deletion in KCNQ1, involving exons 7 and 8. Both variants were confirmed by alternative techniques. The mother and the brother of the index case were also affected by Long QT Syndrome, and family cosegregation was observed for the KCNQ1 deletion, but not for the TTN variant.
  
  
  
  Next Generation Sequencing technology allows a comprehensive genetic analysis of arrhythmogenic diseases. We report a copy number variation identified using Next Generation Sequencing analysis in Long QT Syndrome. Clinical and familiar correlation is crucial to elucidate the role of genetic variants identified to distinguish the pathogenic ones from genetic noise.
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Georgia
authors.initials: G
authors.lastname: Sarquella-Brugada
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Mademont-Soler
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Catarina
authors.initials: C
authors.lastname: Allegue
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Cesar
authors.affiliation: Gendiag SL, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Ferrer-Costa
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Coll
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Mates
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain; Cardiology Service, Hospital Josep Trueta, Girona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D000293:Adolescent; D064211:Connectin / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D010375:Pedigree
chemical_list: D064211:Connectin; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C577285:TTN protein, human