New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants.
作者： Charlotte Andreasen , Jonas B Nielsen , Lena Refsgaard , Anders G Holst , Alex H Christensen
关键词:
摘要: Cardiomyopathies are a heterogeneous group of diseases with various etiologies. We focused on three genetically determined cardiomyopathies: hypertrophic (HCM), dilated (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC). Eighty-four genes have so far been associated these cardiomyopathies, but the disease-causing effect reported variants is often dubious. In order to identify possible false-positive variants, we investigated prevalence previously cardiomyopathy-associated in recently published exome data. searched for missense nonsense NHLBI-Go Exome Sequencing Project (ESP) containing data from 6500 individuals. ESP, identified 94 out 687 (14%) HCM, 58 337 (17%) DCM, 38 209 (18%) ARVC. These findings correspond genotype 1:4 1:6 1:5 PolyPhen-2 predictions were conducted all variants. found significant overrepresentation predicted as being benign among those present ESP compared ones not present. validate our findings, seven genotyped control population this revealed frequencies comparable ESP. conclusion, prevalences up more than one thousand times higher expected phenotype general (HCM 1:500, DCM 1:2500, ARVC 1:5000) suggest that high number monogenic causes cardiomyopathy.
nature.com
researchgate.net 
sci-hub.se 参考文章(30)
Adam Pleister, Randell K Wexler, David Feldman, Terry Elton, Cardiomyopathy: an overview. American Family Physician. ,vol. 79, pp. 778- 784 ,(2009)
Ali J Marian, S. Lutucuta, L. Salek, Molecular genetics and pathogenesis of hypertrophic cardiomyopathy. Minerva Medica. ,vol. 92, pp. 435- 451 ,(2001)
K. Gear, R. Hauer, A. Nava, M. H. Picard, N. Protonotarios, J. E. Saffitz, D. M. Y. Sanborn, J. S. Steinberg, H. Tandri, G. Thiene, J. A. Towbin, A. Tsatsopoulou, T. Wichter, W. Zareba, F. I. Marcus, W. J. McKenna, D. Sherrill, C. Basso, B. Bauce, D. A. Bluemke, H. Calkins, D. Corrado, M. G.P.J. Cox, J. P. Daubert, G. Fontaine, Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia European Heart Journal. ,vol. 31, pp. 806- 814 ,(2010) , 10.1093/EURHEARTJ/EHQ025
Akinori Kimura, Molecular basis of hereditary cardiomyopathy: abnormalities in calcium sensitivity, stretch response, stress response and beyond. Journal of Human Genetics. ,vol. 55, pp. 81- 90 ,(2010) , 10.1038/JHG.2009.138
Ralph Knöll, Masahiko Hoshijima, Hal M. Hoffman, Veronika Person, Ilka Lorenzen-Schmidt, Marie-Louise Bang, Takeharu Hayashi, Nobuyuki Shiga, Hideo Yasukawa, Wolfgang Schaper, William McKenna, Mitsuhiro Yokoyama, Nicholas J. Schork, Jeffrey H. Omens, Andrew D. McCulloch, Akinori Kimura, Carol C. Gregorio, Wolfgang Poller, Jutta Schaper, Heinz P. Schultheiss, Kenneth R. Chien, The Cardiac Mechanical Stretch Sensor Machinery Involves a Z Disc Complex that Is Defective in a Subset of Human Dilated Cardiomyopathy Cell. ,vol. 111, pp. 943- 955 ,(2002) , 10.1016/S0092-8674(02)01226-6
Lena Refsgaard, Anders G Holst, Golnaz Sadjadieh, Stig Haunsø, Jonas B Nielsen, Morten S Olesen, None, High prevalence of genetic variants previously associated with LQT syndrome in new exome data European Journal of Human Genetics. ,vol. 20, pp. 905- 908 ,(2012) , 10.1038/EJHG.2012.23
Bhagyalaxmi Mohapatra, Shinawe Jimenez, Jiuann Huey Lin, Karla R Bowles, Karen J Coveler, Joseph G Marx, Michele A Chrisco, Ross T Murphy, Paul R Lurie, Robert J Schwartz, Perry M Elliott, Matteo Vatta, William McKenna, Jeffrey A Towbin, Neil E Bowles, Mutations in the muscle LIM protein and α-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis Molecular Genetics and Metabolism. ,vol. 80, pp. 207- 215 ,(2003) , 10.1016/S1096-7192(03)00142-2
Morten S Olesen, Anders G Holst, Javad Jabbari, Jonas B Nielsen, Ingrid E Christophersen, Ahmad Sajadieh, Stig Haunsø, Jesper H Svendsen, None, Genetic Loci on Chromosomes 4q25, 7p31, and 12p12 Are Associated With Onset of Lone Atrial Fibrillation Before the Age of 40 Years Canadian Journal of Cardiology. ,vol. 28, pp. 191- 195 ,(2012) , 10.1016/J.CJCA.2011.11.016
Akinori Kimura, Molecular etiology and pathogenesis of hereditary cardiomyopathy. Japanese Circulation Journal-english Edition. ,vol. 72, ,(2008) , 10.1253/CIRCJ.CJ-08-0050
Annukka M. Lahtinen, Eero Lehtonen, Annukka Marjamaa, Maija Kaartinen, Tiina Heliö, Kimmo Porthan, Lasse Oikarinen, Lauri Toivonen, Heikki Swan, Antti Jula, Leena Peltonen, Aarno Palotie, Veikko Salomaa, Kimmo Kontula, Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy Heart Rhythm. ,vol. 8, pp. 1214- 1221 ,(2011) , 10.1016/J.HRTHM.2011.03.015