Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy

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art_MARSIGLIA_Screening_of_MYH7_MYBPC3_and_TNNT2_genes_in_2013.PDF (451.13 KB)
Citações na Scopus
39
Tipo de produção
article
Data de publicação
2013
DOI
Scopus
Web of Science
PubMed
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Título do Volume
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MOSBY-ELSEVIER
Autores
CREDIDIO, Flavia Laghi
REIS, Rafael Ferreira
ARAUJO, Aloir Queiroz de
PEDROSA, Rodrigo Pinto
BARBOSA-FERREIRA, Joao Marcos Bemfica
Citação
AMERICAN HEART JOURNAL, v.166, n.4, p.775-782, 2013
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Background Hypertrophic cardiomyopathy (HC) is the most prevalent genetic cardiac disease caused by a mutation in sarcomeres, Z-disks, or calcium-handling genes and is characterized by unexplained left ventricular hypertrophy. The aim of this study was to determine the genetic profile of Brazilian patients with HC and correlate the genotype with the phenotype. Methods We included 268 index patients from Sao Paulo city and 3 other cities in Brazil and extracted their DNA from whole blood. We amplified the coding sequencing of MYH7, MYBPC3, and TNNT2 genes and sequenced them with an automatic sequencer. Results We identified causal mutations in 131 patients (48.8%). Seventy-eight (59.5%) were in the MYH7 gene, 50 (38.2%) in the MYBPC3 gene, and 3 (2.3%) in the TNNT2 gene. We identified 69 mutations, 24 not previously described. Patients with an identified mutation were younger at diagnosis and at current age, had a higher mean heart rate and higher nonsustained ventricular tachycardia frequency compared with those without a mutation. Patients with MYH7 gene mutations had a larger left atrium and higher frequency of atrial fibrillation than did patients with MYBPC3 gene mutations. Conclusion The presence of a mutation in one of the genes suggests a worse prognosis. Mutations in the MYH7 gene, rather than in the MYBPC3 gene, were also related to a worse prognosis. This is the first work characterizing HC molecular epidemiology in the Brazilian population for the 3 most important genes.
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URI
https://observatorio.fm.usp.br/handle/OPI/3955
Referências
  1. Adzhubei IA, 2010, NAT METHODS, V7, P248, DOI 10.1038/nmeth0410-248
  2. Arteaga E, 2005, AM HEART J, V149, P1099, DOI 10.1016/j.ahj.2004.09.049
  3. Bos JM, 2009, J AM COLL CARDIOL, V54, P201, DOI 10.1016/j.jacc.2009.02.075
  4. Enjuto M, 2000, J MOL CELL CARDIOL, V32, P2307, DOI 10.1006/jmcc.2000.1260
  5. Giolo SR, 2012, EUR J HUM GENET, V20, P111, DOI 10.1038/ejhg.2011.144
  6. Girolami F, 2006, J CARDIOVASC MED, V7, P601
  7. Harris SP, 2002, CIRC RES, V90, P594, DOI 10.1161/01.RES.0000012222.70819.64
  8. HENRY WL, 1980, CIRCULATION, V62, P212
  9. Ho CY, 2010, CIRCULATION, V122, P2430, DOI 10.1161/CIRCULATIONAHA.110.978924
  10. Ingles J, 2005, J MED GENET, V42, DOI 10.1136/jmg.2005.033886
  11. Jaaskelainen P, 2002, J MOL MED-JMM, V80, P412, DOI 10.1007/s00109-002-0323-9
  12. Kelly M, 2009, CIRC-CARDIOVASC GENE, V2, P182, DOI 10.1161/CIRCGENETICS.108.836478
  13. Kumar P, 2009, NAT PROTOC, V4, P1073, DOI 10.1038/nprot.2009.86
  14. Landstrom AP, 2010, CIRCULATION, V122, P2441, DOI 10.1161/CIRCULATIONAHA.110.954446
  15. Maron BJ, 2001, J AM COLL CARDIOL, V38, P315, DOI 10.1016/S0735-1097(01)01386-9
  16. MARON BJ, 1982, CIRCULATION, V65, P1388
  17. MARON BJ, 1995, CIRCULATION, V92, P785
  18. Marsiglia JDC, 2010, ARQ BRAS CARDIOL, V94, P10, DOI 10.1590/S0066-782X2010000100004
  19. Marston S, 2009, CIRC RES, V105, P219, DOI 10.1161/CIRCRESAHA.109.202440
  20. MOOLMAN JC, 1995, HUM MUTAT, V6, P197, DOI 10.1002/humu.1380060219
  21. Moolman-Smook JC, 1999, AM J HUM GENET, V65, P1308, DOI 10.1086/302623
  22. Mora R, 2009, REV ESP CARDIOL, V59, P4
  23. Morner S, 2003, J MOL CELL CARDIOL, V35, P841, DOI 10.1016/S0022-2828(03)00146-9
  24. Olivotto I, 2008, MAYO CLIN PROC, V83, P630, DOI 10.4065/83.6.630
  25. Otsuka H, 2012, CIRC J, V76, P453, DOI 10.1253/circj.CJ-11-0876
  26. Richard P, 2006, J AM COLL CARDIOL, V48, pA79, DOI 10.1016/j.jacc.2006.09.014
  27. Roncarati R, 2011, J CELL PHYSIOL, V226, P2894, DOI 10.1002/jcp.22636
  28. Schwarz JM, 2010, NAT METHODS, V7, P575, DOI 10.1038/nmeth0810-575
  29. Tirone Adriana Paula, 2005, Arq Bras Cardiol, V84, P467, DOI 10.1590/S0066-782X2005000600007
  30. Van Driest SL, 2004, J AM COLL CARDIOL, V44, P602, DOI 10.1016/j.jacc.2004.04.039
  31. Van Driest SL, 2004, J AM COLL CARDIOL, V44, P1903, DOI 10.1016/j.jacc.2004.07.045
  32. Waldmuller S, 2012, EUR J HEART FAIL, V13, P1185
  33. Walsh R, 2009, CARDIOLOGY, V115, P49
  34. Wang SX, 2008, CLIN CARDIOL, V31, P114, DOI 10.1002/clc.20151
  35. Zou YB, 2013, MOL BIOL REP, V40, P3969, DOI 10.1007/s11033-012-2474-2

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/11
Artigos e Materiais de Revistas Científicas - LIM/13