Study of DCM and the Titin Targrt Gene Mutations

作者: 杜 辉 :内蒙古医科大学,内蒙古 呼和浩特; 陈凤英 :内蒙古医科大学附属医院,内蒙古 呼和浩特;

关键词: 扩张型心肌病肌联蛋白RNA结合蛋白20基因突变DCM Titin Rbm20 Gene Mutations

扩张型心肌病(Dilated Cardiomyopathy, DCM)是一种严重危害人们身体健康和生活质量的疾病,其发病隐匿,进展缓慢,初期临床症状不明显,早期诊断较为困难!患者一旦出现明显的临床症状,病情往往已进入不可逆阶段。因此,寻找出一种有效的早期诊断方法,以及尽早建立起一级预防机制显得极其重要!通过研究和探讨与扩张型心肌病相关的肌联蛋白(titin)及RNA结合蛋白20 (RBM20),探讨其突变序列位点,早期干预,能够为扩张型心肌病患者的早期诊断提供重要的依据,具有广阔的应用前景。

Abstract: DCM (Dilated Cardiomyopathy, DCM) is a kind of disease with the characteristics of onset hidden and slow progress, which plays serious damage to the people’s health and life quality. The early clinical symptom is not obvious, so early diagnosis is very difficult! Once somebody gets the obvious clinical symptoms, the disease always has entered the stage of irreversible. As a result, it is extremely important to look for a kind of effective method of early diagnosis to establish primary prevention mechanism quickly. Through the study and exploration of the DCM related titin and Rbm20, we can discuss the locus mutation sequence, do intervention early, to provide important basis in the early diagnosis of patients who have got DCM, has broad application prospects.

文章引用: 杜 辉 , 陈凤英 (2015) 扩张型心肌病与肌联蛋白靶基因突变的研究。 临床医学进展, 5, 50-57. doi: 10.12677/ACM.2015.51010


[1] Karkkainen, S. and Peuhkurinen, K. (2007) Genetics of dilated cardiomyopathy. A comprehensive review of the known genetic mutations that have been shown to cause FDC. Annals of Medicine, 39, 91-107.

[2] Maron, B.J., Towbin, J.A., Thiene, G., et al. (2006) Contemporary definitions and classification of the cardiomyopathies: An American Heart Association scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplanation Committe: Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups: And Council on Epidemiology and Prevention. Circulation, 113, 1807-1816.

[3] Everly, M.J. (2008) Cardiac transplantation in the United States: An analysis of the UNOS registry. Clinical Transplantation, 35-43.

[4] 王玉亭, 王庭槐 (2005) 扩张型心肌病发病机理及治疗进展. 中国心血管杂志, 10, 230-231.

[5] 吕安林, 张晶, 杜娟娟 (2009) 扩张型心肌病发病机制新论. 临床医学工程, 16, 99-100.

[6] 中华医学会心血管病学分会 (2014) 中国心力衰竭诊断和治疗指南2014. 中华心血管病杂志, 42.

[7] Cazeau, S., Leclercq, C., Lavergne, T., et al. (2001) Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. New England Journal of Medicine, 344, 873-880.

[8] Komura, S., Chinushi, M., Kudo, M., et al. (2004) Potential candidates for cardiac resynchronization therapy in Japanese patients with idiopathic dilated cardiomyopathy a Niigatamulticenter study of DCM. Circulation Journal, 68, 1104-1109.

[9] Hosenpud, J.D., Bennett, L.E., Keck, B.M., et al. (1998) The registry of the international society for heart and lung transplantation: Fifteenth official report 1998. The Journal of Heart and Lung Transplantation, 17, 656-668.

[10] 王建安, 谢小洁 (2006) 干细胞移植治疗扩张型心肌病. 中华心血管病杂志, 34, 200-201.

[11] 王虎, 惠汝太 (2006) 基因突变与扩张型心肌病. 中华心血管病杂志, 3, 193-195.

[12] Mestroni, L., Maisch, B., McKenna, W.J., Schwartz, K., Charron, P., Rocco, C., et al. (1999) Guidelines for the study of familial dilated cardiomyopathies. European Heart Journal, 20, 93-102.

[13] Burkelt, E.L. and Hershberger, R.E. (2005) Clinical and genetic issues in familial dilated cardiomyopathy. Journal of the American College of Cardiology, 45, 969-981.

[14] Dunkman, W.B., Johnson, G.R., Carson, P.E., Bhat, G., Farrell, L. and Cohn, J.N. (1993) Incidence of thromboembolic events in congestive heart failure. The V-HeFT VA Cooperative Studies Group. Circulation, 87, UI94-UI101.

[15] Yetino, M., Ozeke, O., Deveci, B., Timur Selcuk, M. and Aras, D. (2006) Multichamber intracardiac thrombi associated with activated protein C resistance in a patient with dilated cardiomyopathy. The International Journal of Cardiovascular Imaging, 22, 59-61.

[16] Staudt, A., Hummel, A., Ruppert, J., Dörr, M., Trimpert, C., Birkenmeier, K., et al. (2006) Immunoadsorption in dilated cardiomyopathy: 6-month results from a randomized study. American Heart Journal, 152, 712el-712e6.

[17] Granzier, H.L. and Labeit, S. (2004) The giant protein titin: A major player in myocardial mechanics, signaling, and disease. Circulation Research, 94, 284-295.

[18] Bang, M.L., Centner, T., Fornoff, F., Geach, A.J., Gotthardt, M., McNabb, M., et al. (2001) The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circulation Research, 89, 1065-1072.

[19] Miller, M.K., Granzier, H., Ehler, E. and Gregorio, C.C. (2004) The sensitive giant: The role of titin-based stretch sensing complexes in the heart. Trends in Cell Biology, 14, 119-126.

[20] Lange, S., Ehler, E. and Gautel, M. (2006) From A to Z and back? Multicompartment proteins in the sarcomere. Trends in Cell Biology, 16, 11-18.

[21] Granzier, H.L. and Irving, T.C. (1995) Passive tension in cardiac muscle: Contribution of collagen, titin, microtubules, and intermediate filaments. Biophysical Journal, 68, 1027-1044.

[22] LeWinter, M.M. (2000) Titin: The “missing link” of diastole. Journal of Molecular and Cellular Cardiology, 32, 2111- 2114.

[23] Cazorla, O., Wu, Y., Irving, T.C. and Granzier, H. (2001) Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes. Circulation Research, 88, 1028-1035.

[24] Helmes, M., Trombitas, K., Granzier, H. (1996) Titin develops restoring force in rat cardiac myocytes. Circulation Research, 79, 619-626.

[25] Hein, S., Kostin, S., Heling, A., Maeno, Y. and Schaper, J. (2000) The role of the cytoskeleton in heart failure. Circulation Research, 45, 273-278.

[26] Gerull, B., Gramlich, M., Atherton, J., McNabb, M., Trombitás, K., Sasse-Klaassen, S., et al. (2002) Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nature Genetics, 30, 201-204.

[27] Guo, W., Schafer, S., Greaser, M.L., Radke, M.H., Liss, M., Govindarajan, T., et al. (2012) RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. Nature Medicine, 18, 766-773.

[28] Li, S., Guo, W., Dewey, C.N. and Greaser, M.L. (2013) Rbm20 regulates titin alternative splicing as a splicing repressor. Nucleic Acids Research, 41, 2659-2672.

[29] Brauch, K.M., Karst, M.L., Herron, K.J., de Andrade, M., Pellikka, P.A., Rodeheffer, R.J., et al. (2009) Mutations in ribonucleic acid binding protein gene cause familial dilated cardiomyopathy. Journal of the American College of Cardiology, 54, 930-941.

[30] Li, D., Morales, A., Gonzalez-Quintana, J., Norton, N., Siegfried, J.D., Hofmeyer, M. and Hershberger, R.E. (2010) Identification of novel mutations in RBM20 in patients with dilated cardiomyopathy. Clinical and Translational Science, 3, 90-97.

[31] Refaat, M.M., Lubitz, S.A., Makino, S., Islam, Z., Frangiskakis, J.M., Mehdi, H., et al. (2012) Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart Rhythm, 9, 390-396.

[32] 王铜 (2012) 克山病监测之转化流行病学. 国外医学医学地理分册, 3, 143-147.

[33] 李兆祥, 杨林, 赵溯, 黄文丽, 王跃兵, 杨鹏 (2012) 2010 年云南省克山病监测结果分析. 国外医学: 医学地理分册, 1, 26-29.

[34] 王斌, 王盼, 雷艳霞 (2013) 硒的功能与心血管疾病的研究进展. 国外医学: 医学地理分册, 1, 20-22.