Investigação de variantes gênicas de canais iônicos em pacientes com síndrome do QT longo

Ernesto Curty, Fernando Eugênio dos Santos Cruz, Fabiane Santos Lima, Jorge Luiz Albuquerque Coutinho, Rosane Silva, Turán Peter Ürményi, Antônio Carlos Campos Carvalho, Edson Rondinelli
2011 Arquivos Brasileiros de Cardiologia  
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,
more » ... f genes KCNQ1, KCNH2 and SCN5A in patients with LQTS and their family members were sequenced and analyzed using Geneious Pro™ software. Results: Two families with clinical criteria for LQTS were investigated. The proband of Family A had QT C = 562 ms, Schwartz Score = 5.5. The genotyping identified the G1714A mutation in the KCNH2 gene. QT C = 521 ± 42 ms was observed in family members carrying the mutation against QT C = 391 ± 21 ms for non-carriers. The proband of Family B had QT C = 551 ms, Schwartz Score = 5.5. The genotyping identified the G1600T mutation, in the same gene. The analysis of family members revealed QT C = 497 ± 42 ms in mutation carriers, compared with QT C = 404 ± 29 ms in non-carriers. Conclusion: 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. (Arq Bras Cardiol 2011;96(3):172-178) Keywords: Long QT syndrome; ion channels; mutation; death sudden cardiac. sudden death 14 , triggers for arrhythmia episodes 15,16 and response to drug treatment 17,18 . Furthermore, the severity depends on the affected region of the channel 19 . That is why the identification of the mutation is important for managing the disease. Despite the large number of variants involved, the search for gene variants associated with LQTS (genotyping) is being increasingly used in clinical practice. To the best of our knowledge, no unit of the National Health System is currently conducting the genotyping of LQTS. For this reason, the gene variants associated with LQTS were investigated in two families clinically diagnosed with the disease. The conditions for the genotyping of genes KCNQ1, KCNH2 and SCN5A were established, and a computational analysis was used to facilitate the identification of mutations previously described and novel gene variants in the Brazilian population. Methods Patients Patients referred to the National Institute of Cardiology with clinical suspicion of LQTS had their medical history Arq Bras Cardiol 2011;96(3):172-178 Curty et al Detection of gene variants in LQTS
doi:10.1590/s0066-782x2011005000015 pmid:21308345 fatcat:uyy7vbuimzhxznnmisng3rv2ra