title: Investigation of ion channel gene variants in patients with long QT syndrome.
abstract: BACKGROUND
  The long QT syndrome (LQTS) is an inherited arrhythmia syndrome with increased QT interval and risk of sudden death. Mutations in genes KCNQ1, KCNH2 and SCN5A account for 90% of cases with genotype determined, and genotyping is informative for genetic counseling and better disease management.
  
  
  OBJECTIVE
  Molecular investigation and computational analysis of gene variants of KCNQ1, KCNH2 and SCN5A associated with LQTS, in families with the disease.
  
  
  METHODS
  The coding regions of genes KCNQ1, KCNH2 and SCN5A in patients with LQTS and their family members were sequenced and analyzed using Geneious ProTM software.
  
  
  RESULTS
  Two families with clinical criteria for LQTS were investigated. The proband of Family A had QTC = 562 ms, Schwartz Score = 5.5. The genotyping identified the G1714A mutation in the KCNH2 gene. QTC = 521 ± 42 ms was observed in family members carrying the mutation against QTC = 391 ± 21 ms for non-carriers. The proband of Family B had QTc = 551 ms, Schwartz Score = 5.5. The genotyping identified the G1600T mutation, in the same gene. The analysis of family members revealed QTC = 497 ± 42 ms in mutation carriers, compared with QTC = 404 ± 29 ms in non-carriers.
  
  
  CONCLUSIONS
  Two gene variants previously associated with LQTS were found in two families clinically diagnosed with LQTS. The prolongation of the QT interval was observed in all family members carrying the mutations. A strategy was developed to identify variants of genes KCNQ1, KCNH2 and SCN5A, making it possible to train technical staff for future application to diagnosis routine.
authors.affiliation: Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rua Evaristo da Veiga 83/509, Rio de Janeiro, RJ, Brazil. ernestocurty@biof.ufrj.br
authors.forename: Curty
authors.initials: C
authors.lastname: Ernesto
authors.forename: Fernando Eugênio dos Santos
authors.initials: FE
authors.lastname: Cruz
authors.forename: Fabiane Santos
authors.initials: FS
authors.lastname: Lima
authors.forename: Jorge Luiz Albuquerque
authors.initials: JL
authors.lastname: Coutinho
authors.forename: Rosane
authors.initials: R
authors.lastname: Silva
authors.forename: Turán Peter
authors.initials: TP
authors.lastname: Urményi
authors.forename: Antônio Carlos Campos
authors.initials: AC
authors.lastname: Carvalho
authors.forename: Edson
authors.initials: E
authors.lastname: Rondinelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000209:etiology; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D017422:Sequence Analysis, DNA / Q000379:methods; D015222:Sodium Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels