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A low prevalence of sarcomeric gene variants in a Chinese cohort with left ventricular non-compaction

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Abstract

Left ventricular non-compaction (LVNC) is genetically heterogeneous. It has been previously shown that LVNC is associated with defects in TAZ, DNTA, LDB3, YWHAE, MIB1, PRDM16, and sarcomeric genes. This study was aimed to investigate sarcomeric gene mutations in a Chinese population with LVNC. From 2004 to 2010, 57 unrelated Chinese patients with LVNC were recruited at Fuwai Hospital, Beijing, China. Detailed clinical evaluation was performed on the probands and available family members. DNA samples isolated from the peripheral blood of the index cases were screened for 10 sarcomeric genes, including MYH7, MYBPC3, MYL2, MYL3, MYH6, TNNC1, TNNT2, TNNI3, TPM1, and ACTC1. Seven heterozygous mutations (6 missense and 1 deletion) were identified in 7 (12 %) of the patients. These mutations were distributed among 4 genes, 4 in MYH7, and 1 each in ACTC1, TNNT2, and TPM1. Six of the mutations were novel and another one was reported previously. All mutations affected conserved amino acid residues and were predicted to alter the structure of the proteins by in silico analysis. No significant difference was observed between mutation-positive and mutation-negative patients with respect to clinical characteristics at baseline and mortality during follow-up. In conclusion, our study indicates that sarcomeric gene mutations are uncommon causes of LVNC in Chinese patients and genetic background of the disease may be divergent among the different races.

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References

  1. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB (2006) Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113(14):1807–1816

    Article  PubMed  Google Scholar 

  2. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, Dubourg O, Kuhl U, Maisch B, McKenna WJ, Monserrat L, Pankuweit S, Rapezzi C, Seferovic P, Tavazzi L, Keren A (2008) Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 29(2):270–276

    Article  PubMed  Google Scholar 

  3. Oechslin EN, Attenhofer Jost CH, Rojas JR, Kaufmann PA, Jenni R (2000) Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol 36(2):493–500

    Article  CAS  PubMed  Google Scholar 

  4. Stanton C, Bruce C, Connolly H, Brady P, Syed I, Hodge D, Asirvatham S, Friedman P (2009) Isolated left ventricular noncompaction syndrome. Am J Cardiol 104(8):1135–1138

    Article  PubMed  Google Scholar 

  5. Aras D, Tufekcioglu O, Ergun K, Ozeke O, Yildiz A, Topaloglu S, Deveci B, Sahin O, Kisacik HL, Korkmaz S (2006) Clinical features of isolated ventricular noncompaction in adults long-term clinical course, echocardiographic properties, and predictors of left ventricular failure. J Card Fail 12(9):726–733

    Article  PubMed  Google Scholar 

  6. Oechslin E, Jenni R (2011) Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity? Eur Heart J 32(12):1446–1456

    Article  PubMed  Google Scholar 

  7. Stollberger C, Blazek G, Wegner C, Winkler-Dworak M, Finsterer J (2011) Neuromuscular and cardiac comorbidity determines survival in 140 patients with left ventricular hypertrabeculation/noncompaction. Int J Cardiol 150(1):71–74

    Article  PubMed  Google Scholar 

  8. Habib G, Charron P, Eicher JC, Giorgi R, Donal E, Laperche T, Boulmier D, Pascal C, Logeart D, Jondeau G, Cohen-Solal A (2011) Isolated left ventricular non-compaction in adults: clinical and echocardiographic features in 105 patients. Results from a French registry. Eur J Heart Fail 13(2):177–185

    Article  PubMed  Google Scholar 

  9. Tian T, Liu Y, Gao L, Wang J, Sun K, Zou Y, Wang L, Zhang L, Li Y, Xiao Y, Song L, Zhou X (2013) Isolated left ventricular noncompaction: clinical profile and prognosis in 106 adult patients. Heart Vessel. doi:10.1007/s00380-013-0409-z

    Google Scholar 

  10. Greutmann M, Mah ML, Silversides CK, Klaassen S, Attenhofer Jost CH, Jenni R, Oechslin EN (2012) Predictors of adverse outcome in adolescents and adults with isolated left ventricular noncompaction. Am J Cardiol 109(2):276–281

    Article  PubMed  Google Scholar 

  11. Bleyl SB, Mumford BR, Thompson V, Carey JC, Pysher TJ, Chin TK, Ward K (1997) Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am J Hum Genet 61(4):868–872

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Ichida F, Tsubata S, Bowles KR, Haneda N, Uese K, Miyawaki T, Dreyer WJ, Messina J, Li H, Bowles NE, Towbin JA (2001) Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation 103(9):1256–1263

    Article  CAS  PubMed  Google Scholar 

  13. Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, Sinagra G, Lin JH, Vu TM, Zhou Q, Bowles KR, Di Lenarda A, Schimmenti L, Fox M, Chrisco MA, Murphy RT, McKenna W, Elliott P, Bowles NE, Chen J, Valle G, Towbin JA (2003) Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. J Am Coll Cardiol 42(11):2014–2027

    Article  CAS  PubMed  Google Scholar 

  14. Luxan G, Casanova JC, Martinez-Poveda B, Prados B, D’Amato G, MacGrogan D, Gonzalez-Rajal A, Dobarro D, Torroja C, Martinez F, Izquierdo-Garcia JL, Fernandez-Friera L, Sabater-Molina M, Kong YY, Pizarro G, Ibanez B, Medrano C, Garcia-Pavia P, Gimeno JR, Monserrat L, Jimenez-Borreguero LJ, de la Pompa JL (2013) Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy. Nat Med 19(2):193–201

    Article  CAS  PubMed  Google Scholar 

  15. Arndt AK, Schafer S, Drenckhahn JD, Sabeh MK, Plovie ER, Caliebe A, Klopocki E, Musso G, Werdich AA, Kalwa H, Heinig M, Padera RF, Wassilew K, Bluhm J, Harnack C, Martitz J, Barton PJ, Greutmann M, Berger F, Hubner N, Siebert R, Kramer HH, Cook SA, Macrae CA, Klaassen S (2013) Fine Mapping of the 1p36 Deletion Syndrome Identifies Mutation of PRDM16 as a Cause of Cardiomyopathy. Am J Hum Genet 93(1):67–77

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Chang B, Gorbea C, Lezin G, Li L, Shan L, Sakai N, Kogaki S, Otomo T, Okinaga T, Hamaoka A, Yu X, Hata Y, Nishida N, Yost HJ, Bowles NE, Brunelli L, Ichida F (2013) 14-3-3epsilon gene variants in a Japanese patient with left ventricular noncompaction and hypoplasia of the corpus callosum. Gene 515(1):173–180

    Article  CAS  PubMed  Google Scholar 

  17. Tian T, Liu Y, Zhou X, Song L (2013) Progress in the molecular genetics of hypertrophic cardiomyopathy: a mini-review. Gerontology 59(3):199–205

    Article  CAS  PubMed  Google Scholar 

  18. Kawashiri MA, Hayashi K, Konno T, Fujino N, Ino H, Yamagishi M (2013) Current perspectives in genetic cardiovascular disorders: from basic to clinical aspects. Heart Vessel. doi:10.1007/s00380-013-0391-5

    Google Scholar 

  19. Hershberger RE, Siegfried JD (2011) Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol 57(16):1641–1649

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. McNally EM, Golbus JR, Puckelwartz MJ (2013) Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest 123(1):19–26

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Monserrat L, Hermida-Prieto M, Fernandez X, Rodriguez I, Dumont C, Cazon L, Cuesta MG, Gonzalez-Juanatey C, Peteiro J, Alvarez N, Penas-Lado M, Castro-Beiras A (2007) Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects. Eur Heart J 28(16):1953–1961

    Article  CAS  PubMed  Google Scholar 

  22. Hoedemaekers YM, Caliskan K, Majoor-Krakauer D, van de Laar I, Michels M, Witsenburg M, ten Cate FJ, Simoons ML, Dooijes D (2007) Cardiac beta-myosin heavy chain defects in two families with non-compaction cardiomyopathy: linking non-compaction to hypertrophic, restrictive, and dilated cardiomyopathies. Eur Heart J 28(22):2732–2737

    Article  CAS  PubMed  Google Scholar 

  23. Luedde M, Ehlermann P, Weichenhan D, Will R, Zeller R, Rupp S, Muller A, Steen H, Ivandic BT, Ulmer HE, Kern M, Katus HA, Frey N (2010) Severe familial left ventricular non-compaction cardiomyopathy due to a novel troponin T (TNNT2) mutation. Cardiovasc Res 86(3):452–460

    Article  CAS  PubMed  Google Scholar 

  24. Dellefave LM, Pytel P, Mewborn S, Mora B, Guris DL, Fedson S, Waggoner D, Moskowitz I, McNally EM (2009) Sarcomere mutations in cardiomyopathy with left ventricular hypertrabeculation. Circ Cardiovasc Genet 2(5):442–449

    Article  CAS  PubMed  Google Scholar 

  25. Chang B, Nishizawa T, Furutani M, Fujiki A, Tani M, Kawaguchi M, Ibuki K, Hirono K, Taneichi H, Uese K, Onuma Y, Bowles NE, Ichida F, Inoue H, Matsuoka R, Miyawaki T (2011) Identification of a novel TPM1 mutation in a family with left ventricular noncompaction and sudden death. Mol Genet Metab 102(2):200–206

    Article  PubMed  Google Scholar 

  26. Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA (2001) Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart 86(6):666–671

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Klaassen S, Probst S, Oechslin E, Gerull B, Krings G, Schuler P, Greutmann M, Hurlimann D, Yegitbasi M, Pons L, Gramlich M, Drenckhahn JD, Heuser A, Berger F, Jenni R, Thierfelder L (2008) Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation 117(22):2893–2901

    Article  CAS  PubMed  Google Scholar 

  28. Probst S, Oechslin E, Schuler P, Greutmann M, Boye P, Knirsch W, Berger F, Thierfelder L, Jenni R, Klaassen S (2011) Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype. Circ Cardiovasc Genet 4(4):367–374

    Article  CAS  PubMed  Google Scholar 

  29. Hoedemaekers YM, Caliskan K, Michels M, Frohn-Mulder I, van der Smagt JJ, Phefferkorn JE, Wessels MW, ten Cate FJ, Sijbrands EJ, Dooijes D, Majoor-Krakauer DF (2010) The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy. Circ Cardiovasc Genet 3(3):232–239

    Article  PubMed  Google Scholar 

  30. Moller DV, Andersen PS, Hedley P, Ersboll MK, Bundgaard H, Moolman-Smook J, Christiansen M, Kober L (2009) The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy. Eur J Hum Genet 17(10):1241–1249

    Article  PubMed Central  PubMed  Google Scholar 

  31. Ripoll Vera T, Monserrat Iglesias L, Hermida Prieto M, Ortiz M, Rodriguez Garcia I, Govea Callizo N, Gomez Navarro C, Rosell Andreo J, Gamez Martinez JM, Pons Llado G, Cremer Luengos D, Torres Marques J (2010) The R820W mutation in the MYBPC3 gene, associated with hypertrophic cardiomyopathy in cats, causes hypertrophic cardiomyopathy and left ventricular non-compaction in humans. Int J Cardiol 145(2):405–407

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank all patients for participating in this study. This work was supported by the Ministry of Science and Technology of China (grant Nos. 2009DFB30050 and 2010CB732601), the National Natural Science Foundation of China (grant No. 30971233) and the Specialized Research Fund for the Doctoral Program of Higher Education of China (grant No. 20131106120009).

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Authors and Affiliations

  1. Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, People’s Republic of China

    Tao Tian, Yilu Wang, Lei Jia & Yubao Zou

  2. Sino-German Laboratory for Molecular Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, People’s Republic of China

    Jizheng Wang, Hu Wang, Kai Sun & Rutai Hui

  3. Hypertension Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, People’s Republic of China

    Xianliang Zhou & Lei Song

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  1. Tao Tian
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Correspondence to Xianliang Zhou or Lei Song.

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Tian, T., Wang, J., Wang, H. et al. A low prevalence of sarcomeric gene variants in a Chinese cohort with left ventricular non-compaction. Heart Vessels 30, 258–264 (2015). https://doi.org/10.1007/s00380-014-0503-x

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  • DOI: https://doi.org/10.1007/s00380-014-0503-x

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