FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 338:1248-1257 April 30, 1998 Number 18 Next

	Full Text PDF Editorial by Sutton, M. St. J. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Mutations in the gene for cardiac myosin-binding protein C account for approximately 15 percent of cases of familial hypertrophic cardiomyopathy. The spectrum of disease-causing mutations and the associated clinical features of these gene defects are unknown.

Methods DNA sequences encoding cardiac myosin-binding protein C were determined in unrelated patients with familial hypertrophic cardiomyopathy. Mutations were found in 16 probands, who had 574 family members at risk of inheriting these defects. The genotypes of these family members were determined, and the clinical status of 212 family members with mutations in the gene for cardiac myosin-binding protein C was assessed.

Results Twelve novel mutations were identified in probands from 16 families. Four were missense mutations; eight defects (insertions, deletions, and splice mutations) were predicted to truncate cardiac myosin-binding protein C. The clinical expression of either missense or truncation mutations was similar to that observed for other genetic causes of hypertrophic cardiomyopathy, but the age at onset of the disease differed markedly. Only 58 percent of adults under the age of 50 years who had a mutation in the cardiac myosin-binding protein C gene (68 of 117 patients) had cardiac hypertrophy; disease penetrance remained incomplete through the age of 60 years. Survival was generally better than that observed among patients with hypertrophic cardiomyopathy caused by other mutations in the genes for sarcomere proteins. Most deaths due to cardiac causes in these families occurred suddenly.

Conclusions The clinical expression of mutations in the gene for cardiac myosin-binding protein C is often delayed until middle age or old age. Delayed expression of cardiac hypertrophy and a favorable clinical course may hinder recognition of the heritable nature of mutations in the cardiac myosin-binding protein C gene. Clinical screening in adult life may be warranted for members of families characterized by hypertrophic cardiomyopathy.

Source Information

From the Howard Hughes Medical Institute and the Department of Genetics, Harvard Medical School, Boston (H.N., S.S., J.G.S.); the First Department of Internal Medicine, Kagoshima University, Kagoshima, Japan (H.N.); the Molecular Cardiology Unit, Department of Medicine, Baylor College of Medicine, Houston (L.L.B., R.R.); the University of Oxford, Oxford, United Kingdom (H.W.); the Departments of Pediatrics and Human Genetics, University of Manitoba, and the Section of Genetics and Metabolism, Children's Hospital — both in Winnipeg, Canada (A.E.C.); the Department of Cardiological Sciences, St. George's Hospital Medical School, London (W.M.); the Department of Medicine, University Hospital, Reykjavik, Iceland (A.K.); the Center for Cardiovascular Research, Toronto Hospital, University of Toronto, Toronto (M.S.); the Cardiovascular Research Division, Minneapolis Heart Institute Foundation, Minneapolis (B.J.M.); and Howard Hughes Medical Institute and the Cardiovascular Division, Brigham and Women's Hospital, Boston (C.E.S.). Other authors were Ludwig Thierfelder, M.D., Max Delbruck Center for Molecular Medicine, Berlin-Buch, Germany; John A. Jarcho, M.D., Cardiovascular Division, Brigham and Women's Hospital, Boston; Aris Anastasakis, M.D., and Pavlos Toutouzas, M.D., Department of Cardiology, University of Athens, Hippokration Hospital, Athens, Greece; Eleanor Elstein, M.D., Center for Cardiovascular Research, Toronto Hospital, University of Toronto, Toronto, and Division of Cardiology, Royal Victoria Hospital, Montreal; Choong-Chin Liew, Ph.D., Jack Liew, Ph.D., John Mably, Ph.D., Harry Rakowski, M.D., E. Douglas Wigle, M.D., and Minshun Zhao, Ph.D., Center for Cardiovascular Research, Toronto Hospital, University of Toronto, Toronto; Rosemarie Salerni, M.D., University of Pittsburgh–Veterans Affairs Medical Center, Pittsburgh; and Halldora Bjornsdottir, M.D., Division of Cardiology, University Hospital, Reykjavik, Iceland.

Address reprint requests to Dr. Christine Seidman at the Department of Genetics, Alpert Rm. 533, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115.

Full Text of this Article

This article has been cited by other articles:

• Martin, M., Reguero, J. J. R., Castro, M. G., Coto, E., Hernandez, E., Carro, A., Calvo, D., Mori de la Tassa, C. (2008). Hypertrophic cardiomyopathy and athlete's heart: a tale of two entities. Eur J Echocardiogr 0: jen219v1-3 [Abstract] [Full Text]  
• Leatherbury, L., Yu, Q., Chatterjee, B., Walker, D. L., Yu, Z., Tian, X., Lo, C. W. (2008). A novel mouse model of X-linked cardiac hypertrophy. Am. J. Physiol. Heart Circ. Physiol. 294: H2701-H2711 [Abstract] [Full Text]  
• Morita, H., Rehm, H. L., Menesses, A., McDonough, B., Roberts, A. E., Kucherlapati, R., Towbin, J. A., Seidman, J.G., Seidman, C. E. (2008). Shared Genetic Causes of Cardiac Hypertrophy in Children and Adults. NEJM 358: 1899-1908 [Abstract] [Full Text]  
• Pelliccia, A., Di Paolo, F. M., Quattrini, F. M., Basso, C., Culasso, F., Popoli, G., De Luca, R., Spataro, A., Biffi, A., Thiene, G., Maron, B. J. (2008). Outcomes in Athletes with Marked ECG Repolarization Abnormalities. NEJM 358: 152-161 [Abstract] [Full Text]  
• Hansen, M. W., Merchant, N. (2007). MRI of Hypertrophic Cardiomyopathy: Part I, MRI Appearances. Am. J. Roentgenol. 189: 1335-1343 [Abstract] [Full Text]  
• Hansen, M. W., Merchant, N. (2007). MRI of Hypertrophic Cardiomyopathy: Part 2, Differential Diagnosis, Risk Stratification, and Posttreatment MRI Appearances. Am. J. Roentgenol. 189: 1344-1352 [Abstract] [Full Text]  
• Nagayama, T., Takimoto, E., Sadayappan, S., Mudd, J. O., Seidman, J.G., Robbins, J., Kass, D. A. (2007). Control of In Vivo Contraction/Relaxation Kinetics by Myosin Binding Protein C: Protein Kinase A Phosphorylation Dependent and Independent Regulation. Circulation 116: 2399-2408 [Abstract] [Full Text]  
• Sen-Chowdhry, S., Syrris, P., McKenna, W. J. (2007). Role of Genetic Analysis in the Management of Patients With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. J Am Coll Cardiol 50: 1813-1821 [Abstract] [Full Text]  
• Daw, E. W., Chen, S. N., Czernuszewicz, G., Lombardi, R., Lu, Y., Ma, J., Roberts, R., Shete, S., Marian, A. J. (2007). Genome-wide mapping of modifier chromosomal loci for human hypertrophic cardiomyopathy. Hum Mol Genet 16: 2463-2471 [Abstract] [Full Text]  
• Kulikovskaya, I., McClellan, G. B., Levine, R., Winegrad, S. (2007). Multiple Forms of Cardiac Myosin-binding Protein C Exist and Can Regulate Thick Filament Stability. J. Gen. Physiol. 129: 419-428 [Abstract] [Full Text]  
• Bella, J. N., Tang, W., Kraja, A., Rao, D. C., Hunt, S. C., Miller, M. B., Palmieri, V., Roman, M. J., Kitzman, D. W., Oberman, A., Devereux, R. B., Arnett, D. K. (2007). Genome-Wide Linkage Mapping for Valve Calcification Susceptibility Loci in Hypertensive Sibships: The Hypertension Genetic Epidemiology Network Study. Hypertension 49: 453-460 [Abstract] [Full Text]  
• Richard, P., Villard, E., Charron, P., Isnard, R. (2006). The Genetic Bases of Cardiomyopathies. J Am Coll Cardiol 48: A79-A89 [Abstract] [Full Text]  
• Morita, H., Larson, M. G., Barr, S. C., Vasan, R. S., O'Donnell, C. J., Hirschhorn, J. N., Levy, D., Corey, D., Seidman, C. E., Seidman, J.G., Benjamin, E. J. (2006). Single-Gene Mutations and Increased Left Ventricular Wall Thickness in the Community: The Framingham Heart Study. Circulation 113: 2697-2705 [Abstract] [Full Text]  
• Song, L., DePalma, S. R., Kharlap, M., Zenovich, A. G., Cirino, A., Mitchell, R., McDonough, B., Maron, B. J., Seidman, C. E., Seidman, J.G., Ho, C. Y. (2006). Novel Locus for an Inherited Cardiomyopathy Maps to Chromosome 7. Circulation 113: 2186-2192 [Abstract] [Full Text]  
• Priori, S. G., Napolitano, C. (2006). Role of Genetic Analyses in Cardiology: Part I: Mendelian Diseases: Cardiac Channelopathies. Circulation 113: 1130-1135 [Abstract] [Full Text]  
• Wolf, C. M., Moskowitz, I. P. G., Arno, S., Branco, D. M., Semsarian, C., Bernstein, S. A., Peterson, M., Maida, M., Morley, G. E., Fishman, G., Berul, C. I., Seidman, C. E., Seidman, J. G. (2005). Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia. Proc. Natl. Acad. Sci. USA 102: 18123-18128 [Abstract] [Full Text]  
• Kubo, T., Kitaoka, H., Okawa, M., Matsumura, Y., Hitomi, N., Yamasaki, N., Furuno, T., Takata, J., Nishinaga, M., Kimura, A., Doi, Y. L. (2005). Lifelong Left Ventricular Remodeling of Hypertrophic Cardiomyopathy Caused by a Founder Frameshift Deletion Mutation in the Cardiac Myosin-Binding Protein C Gene Among Japanese. J Am Coll Cardiol 46: 1737-1743 [Abstract] [Full Text]  
• Ackerman, M. J., Van Driest, S. L., Bos, M. (2005). Are Longitudinal, Natural History Studies the Next Step in Genotype-Phenotype Translational Genomics in Hypertrophic Cardiomyopathy?. J Am Coll Cardiol 46: 1744-1746 [Full Text]  
• Arad, M., Penas-Lado, M., Monserrat, L., Maron, B. J., Sherrid, M., Ho, C. Y., Barr, S., Karim, A., Olson, T. M., Kamisago, M., Seidman, J.G., Seidman, C. E. (2005). Gene Mutations in Apical Hypertrophic Cardiomyopathy. Circulation 112: 2805-2811 [Abstract] [Full Text]  
• Ingles, J, Doolan, A, Chiu, C, Seidman, J, Seidman, C, Semsarian, C (2005). Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. J. Med. Genet. 42: e59-e59 [Abstract] [Full Text]  
• Watkins, H., McKenna, W. J. (2005). The Prognostic Impact of Septal Myectomy in Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol 46: 477-479 [Full Text]  
• Hermida-Prieto, M., Laredo, R., Monserrat, L., Castro-Beiras, A. (2005). Standard Mutation Nomenclature in Hypertrophic Cardiomyopathy: An Urgent Need. J Am Coll Cardiol 46: 380-381 [Full Text]  
• Van Driest, S. L., Vasile, V. C., Ommen, S. R., Will, M. L., Tajik, A. J., Gersh, B. J., Ackerman, M. J. (2005). Reply. J Am Coll Cardiol 46: 381-382 [Full Text]  
• Arad, M., Maron, B. J., Gorham, J. M., Johnson, W. H. Jr., Saul, J. P., Perez-Atayde, A. R., Spirito, P., Wright, G. B., Kanter, R. J., Seidman, C. E., Seidman, J.G. (2005). Glycogen Storage Diseases Presenting as Hypertrophic Cardiomyopathy. NEJM 352: 362-372 [Abstract] [Full Text]  
• Manh, T. P. V., Mokrane, M., Georgenthum, E., Flavigny, J., Carrier, L., Semeriva, M., Piovant, M., Roder, L. (2005). Expression of cardiac myosin-binding protein-C (cMyBP-C) in Drosophila as a model for the study of human cardiomyopathies. Hum Mol Genet 14: 7-17 [Abstract] [Full Text]  
• Mogensen, J., Murphy, R. T., Kubo, T., Bahl, A., Moon, J. C., Klausen, I. C., Elliott, P. M., McKenna, W. J. (2004). Frequency and clinical expression of cardiac troponin I mutations in 748 consecutive families with hypertrophic cardiomyopathy. J Am Coll Cardiol 44: 2315-2325 [Abstract] [Full Text]  
• Kato, T. S., Noda, A., Izawa, H., Yamada, A., Obata, K., Nagata, K., Iwase, M., Murohara, T., Yokota, M. (2004). Discrimination of Nonobstructive Hypertrophic Cardiomyopathy From Hypertensive Left Ventricular Hypertrophy on the Basis of Strain Rate Imaging by Tissue Doppler Ultrasonography. Circulation 110: 3808-3814 [Abstract] [Full Text]  
• Maron, B. J., Seidman, J.G., Seidman, C. E. (2004). Proposal for contemporary screening strategies in families with hypertrophic cardiomyopathy. J Am Coll Cardiol 44: 2125-2132 [Abstract] [Full Text]  
• Gilbert-Barness, E. (2004). Metabolic Cardiomyopathy and Conduction System Defects in Children. Annals of Clinical & Laboratory Science 34: 15-34 [Abstract] [Full Text]  
• Maron, B. J., McKenna, W. J., Danielson, G. K., Kappenberger, L. J., Kuhn, H. J., Seidman, C. E., Shah, P. M., Spencer, W. H. III, Spirito, P., Ten Cate, F. J., Wigle, E. D., Vogel, R. A., Abrams, J., Bates, E. R., Brodie, B. R., Danias, P. G., Gregoratos, G., Hlatky, M. A., Hochman, J. S., Kaul, S., Lichtenberg, R. C., Lindner, J. R., O'rourke, R. A., Pohost, G. M., Schofield, R. S., Tracy, C. M., Winters, W. L. Jr, Klein, W. W., Priori, S. G., Alonso-Garcia, A., Blomstrom-Lundqvist, C., De Backer, G., Deckers, J., Flather, M., Hradec, J., Oto, A., Parkhomenko, A., Silber, S., Torbicki, A. (2003). American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 42: 1687-1713 [Full Text]  
• Writing Committee Members, , Maron, B. J., McKenna, W. J., Danielson, G. K., Kappenberger, L. J., Kuhn, H. J., Seidman, C. E., Shah, P. M., Spencer, W. H. III, Spirito, P., Ten Cate, F. J., Wigle, E. D., ACCF Task Force on Clinical Expert Consensus Docum, , Vogel, R. A., Abrams, J., Bates, E. R., Brodie, B. R., Danias, P. G., Gregoratos, G., Hlatky, M. A., Hochman, J. S., Kaul, S., Lichtenberg, R. C., Lindner, J. R., O'Rourke, R. A., Pohost, G. M., Schofield, R. S., Tracy, C. M., Winters, W. L. Jr, ESC Committee for Practice Guidelines Members, , Klein, W. W., Priori, S. G., Alonso-Garcia, A., Blomstrom-Lundqvist, C., De Backer, G., Deckers, J., Flather, M., Hradec, J., Oto, A., Parkhomenko, A., Silber, S., Torbicki, A. (2003). American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. Eur Heart J 24: 1965-1991 [Full Text]  
• Korte, F. S., McDonald, K. S., Harris, S. P., Moss, R. L. (2003). Loaded Shortening, Power Output, and Rate of Force Redevelopment Are Increased With Knockout of Cardiac Myosin Binding Protein-C. Circ. Res. 93: 752-758 [Abstract] [Full Text]  
• Alders, M., Jongbloed, R., Deelen, W., van den Wijngaard, A., Doevendans, P., Ten Cate, F., Regitz-Zagrosek, V., Vosberg, H.-P., van Langen, I., Wilde, A., Dooijes, D., Mannens, M. (2003). The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands. Eur Heart J 24: 1848-1853 [Abstract] [Full Text]  
• Woo, A, Rakowski, H, Liew, J C, Zhao, M-S, Liew, C-C, Parker, T G, Zeller, M, Wigle, E D, Sole, M J (2003). Mutations of the {beta} myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis. Heart 89: 1179-1185 [Abstract] [Full Text]  
• Maron, B. J., Casey, S. A., Hauser, R. G., Aeppli, D. M. (2003). Clinical course of hypertrophiccardiomyopathy with survival to advanced age. J Am Coll Cardiol 42: 882-888 [Abstract] [Full Text]  
• Garcia-Castro, M., Reguero, J. R., Batalla, A., Diaz-Molina, B., Gonzalez, P., Alvarez, V., Cortina, A., Cubero, G. I., Coto, E. (2003). Hypertrophic Cardiomyopathy: Low Frequency of Mutations in the {beta}-Myosin Heavy Chain (MYH7) and Cardiac Troponin T (TNNT2) Genes among Spanish Patients. Clin. Chem. 49: 1279-1285 [Abstract] [Full Text]  
• Nabel, E. G. (2003). Cardiovascular Disease. NEJM 349: 60-72 [Full Text]  
• Thaman, R, Varnava, A, Hamid, M S, Firoozi, S, Sachdev, B, Condon, M, Gimeno, J R, Murphy, R, Elliott, P M, McKenna, W J (2003). Pregnancy related complications in women with hypertrophic cardiomyopathy. Heart 89: 752-756 [Abstract] [Full Text]  
• Crilley, J. G., Boehm, E. A., Blair, E., Rajagopalan, B., Blamire, A. M., Styles, P., McKenna, W. J., Ostman-Smith, I., Clarke, K., Watkins, H. (2003). Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J Am Coll Cardiol 41: 1776-1782 [Abstract] [Full Text]  
• Marian, A.J., Roberts, R. (2003). To Screen or Not Is Not the Question-- It Is When and How to Screen. Circulation 107: 2171-2174 [Full Text]  
• Marian, A. J. (2003). On predictors of sudden cardiac death in hypertrophic cardiomyopathy. J Am Coll Cardiol 41: 994-996 [Full Text]  
• Konno, T., Shimizu, M., Ino, H., Matsuyama, T., Yamaguchi, M., Terai, H., Hayashi, K., Mabuchi, T., Kiyama, M., Sakata, K., Hayashi, T., Inoue, M., Kaneda, T., Mabuchi, H. (2003). A novel missense mutation in the myosin binding protein-C gene is responsible for hypertrophic cardiomyopathy with left ventricular dysfunction and dilation in elderly patients. J Am Coll Cardiol 41: 781-786 [Abstract] [Full Text]  
• Hengstenberg, C, Erdmann, J, Charron, P (2003). Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac beta-myosin gene mutations: Prediction of clinical status--is molecular genetics a new tool for the management of hypertrophic cardiomyopathy in clinical practice?. Cardiovasc Res 57: 298-301 [Full Text]  
• Havndrup, O., Bundgaard, H., Skytt Andersen, P., Allan Larsen, L., Vuust, J., Kjeldsen, K., Christiansen, M. (2003). Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac {beta}-myosin gene mutations. Cardiovasc Res 57: 347-357 [Abstract] [Full Text]  
• Autore, C., Conte, M. R., Piccininno, M., Bernabo, P., Bonfiglio, G., Bruzzi, P., Spirito, P. (2002). Risk associated with pregnancy in hypertrophic cardiomyopathy. J Am Coll Cardiol 40: 1864-1869 [Abstract] [Full Text]  
• Robbins, J., Benson, D. W. (2002). Structure-Function Relationships in Myosin Binding Protein-C: Taking Off the Blinders and Collaring Hypertrophic Cardiomyopathy. Circ. Res. 91: 656-658 [Full Text]  
• Moolman-Smook, J., Flashman, E., de Lange, W., Li, Z., Corfield, V., Redwood, C., Watkins, H. (2002). Identification of Novel Interactions Between Domains of Myosin Binding Protein-C That Are Modulated by Hypertrophic Cardiomyopathy Missense Mutations. Circ. Res. 91: 704-711 [Abstract] [Full Text]  
• Arad, M., Seidman, J.G., Seidman, C. E. (2002). Phenotypic diversity in hypertrophic cardiomyopathy. Hum Mol Genet 11: 2499-2506 [Abstract] [Full Text]  
• Fatkin, D., Graham, R. M. (2002). Molecular Mechanisms of Inherited Cardiomyopathies. Physiol. Rev. 82: 945-980 [Abstract] [Full Text]  
• Ho, C. Y., Sweitzer, N. K., McDonough, B., Maron, B. J., Casey, S. A., Seidman, J.G., Seidman, C. E., Solomon, S. D. (2002). Assessment of Diastolic Function With Doppler Tissue Imaging to Predict Genotype in Preclinical Hypertrophic Cardiomyopathy. Circulation 105: 2992-2997 [Abstract] [Full Text]  
• Frustaci, A., Pieroni, M., Chimenti, C. (2002). Late-onset primary LVH HCM versus cardiac fabry variant. J Am Coll Cardiol 39: 1405-1406 [Full Text]  
• Maron, B. J., Seidman, J. G., Seidman, C. E. (2002). Late-onset primary LVHHCM versus cardiac fabry variant: reply. J Am Coll Cardiol 39: 1406-1406 [Full Text]  
• Harris, S. P., Bartley, C. R., Hacker, T. A., McDonald, K. S., Douglas, P. S., Greaser, M. L., Powers, P. A., Moss, R. L. (2002). Hypertrophic Cardiomyopathy in Cardiac Myosin Binding Protein-C Knockout Mice. Circ. Res. 90: 594-601 [Abstract] [Full Text]  
• Maron, B. J. (2002). Hypertrophic Cardiomyopathy: A Systematic Review. JAMA 287: 1308-1320 [Abstract] [Full Text]  
• Ortlepp, J R, Vosberg, H P, Reith, S, Ohme, F, Mahon, N G, Schroder, D, Klues, H G, Hanrath, P, McKenna, W J (2002). Genetic polymorphisms in the renin-angiotensin-aldosterone system associated with expression of left ventricular hypertrophy in hypertrophic cardiomyopathy: a study of five polymorphic genes in a family with a disease causing mutation in the myosin binding protein C gene. Heart 87: 270-275 [Abstract] [Full Text]  
• Niimura, H., Patton, K. K., McKenna, W. J., Soults, J., Maron, B. J., Seidman, J.G., Seidman, C. E. (2002). Sarcomere Protein Gene Mutations in Hypertrophic Cardiomyopathy of the Elderly. Circulation 105: 446-451 [Abstract] [Full Text]  
• Li, G., Borger, M. A., Williams, W. G., Weisel, R. D., Mickle, D. A. G., Wigle, E. D., Li, R.-K. (2002). Regional overexpression of insulin-like growth factor-I and transforming growth factor-{beta}1 in the myocardium of patients with hypertrophic obstructive cardiomyopathy. J. Thorac. Cardiovasc. Surg. 123: 89-95 [Abstract] [Full Text]  
• Wigle, E D. (2001). CARDIOMYOPATHY: The diagnosis of hypertrophic cardiomyopathy. Heart 86: 709-714 [Full Text]  
• Berul, C. I., McConnell, B. K., Wakimoto, H., Moskowitz, I. P.G., Maguire, C. T., Semsarian, C., Vargas, M. M., Gehrmann, J., Seidman, C. E., Seidman, J. G. (2001). Ventricular Arrhythmia Vulnerability in Cardiomyopathic Mice With Homozygous Mutant Myosin-Binding Protein C Gene. Circulation 104: 2734-2739 [Abstract] [Full Text]  
• Li, D., Czernuszewicz, G. Z., Gonzalez, O., Tapscott, T., Karibe, A., Durand, J.-B., Brugada, R., Hill, R., Gregoritch, J. M., Anderson, J. L., Quinones, M., Bachinski, L. L., Roberts, R. (2001). Novel Cardiac Troponin T Mutation as a Cause of Familial Dilated Cardiomyopathy. Circulation 104: 2188-2193 [Abstract] [Full Text]  
• Roberts, R., Sigwart, U. (2001). New Concepts in Hypertrophic Cardiomyopathies, Part I. Circulation 104: 2113-2116 [Full Text]  
• Sigwart, U. (2001). Non-surgical myocardial reduction for patients with hypertrophic obstructive cardiomyopathy. Eur Heart J Suppl 3: L38-L42 [Abstract]  
• Watkins, H. (2001). Hypertrophic cardiomyopathy: from molecular and genetic mechanisms to clinical management. Eur Heart J Suppl 3: L43-L50 [Abstract]  
• Arnett, D. K., Devereux, R. B., Kitzman, D., Oberman, A., Hopkins, P., Atwood, L., Dewan, A., Rao, D. C. (2001). Linkage of Left Ventricular Contractility to Chromosome 11 in Humans: The HyperGEN Study. Hypertension 38: 767-772 [Abstract] [Full Text]  
• Varnava, A. M., Elliott, P. M., Baboonian, C., Davison, F., Davies, M. J., McKenna, W. J. (2001). Hypertrophic Cardiomyopathy: Histopathological Features of Sudden Death in Cardiac Troponin T Disease. Circulation 104: 1380-1384 [Abstract] [Full Text]  
• Maron, B. J., Niimura, H., Casey, S. A., Soper, M. K., Wright, G. B., Seidman, J. G., Seidman, C. E. (2001). Development of left ventricular hypertrophy in adults with hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations. J Am Coll Cardiol 38: 315-321 [Abstract] [Full Text]  
• Erdmann, J., Raible, J.o., Maki-Abadi, J., Hummel, M., Hammann, J., Wollnik, B., Frantz, E., Fleck, E., Hetzer, R., Regitz-Zagrosek, V. (2001). Spectrum of clinical phenotypes and gene variants in cardiac myosin-binding protein C mutation carriers with hypertrophic cardiomyopathy. J Am Coll Cardiol 38: 322-330 [Abstract] [Full Text]  
• Marian, A. J. (2001). On genetic and phenotypic variability of hypertrophic cardiomyopathy: nature versus nurture. J Am Coll Cardiol 38: 331-334 [Full Text]  
• Ommen, S. R., Tajik, A. J. (2001). Hypertrophic Cardiomyopathy: From Bedside to Bench ... And Now Back Again?. Circulation 104: 126-127 [Full Text]  
• Nagueh, S. F., Bachinski, L. L., Meyer, D., Hill, R., Zoghbi, W. A., Tam, J. W., Quinones, M. A., Roberts, R., Marian, A.J. (2001). Tissue Doppler Imaging Consistently Detects Myocardial Abnormalities in Patients With Hypertrophic Cardiomyopathy and Provides a Novel Means for an Early Diagnosis Before and Independently of Hypertrophy. Circulation 104: 128-130 [Abstract] [Full Text]  
• Yang, Q., Hewett, T. E., Klevitsky, R., Sanbe, A., Wang, X., Robbins, J. (2001). PKA-dependent phosphorylation of cardiac myosin binding protein C in transgenic mice. Cardiovasc Res 51: 80-88 [Abstract] [Full Text]  
• Spooner, P. M., Albert, C., Benjamin, E. J., Boineau, R., Elston, R. C., George, A. L. Jr, Jouven, X., Kuller, L. H., MacCluer, J. W., Marban, E., Muller, J. E., Schwartz, P. J., Siscovick, D. S., Tracy, R. P., Zareba, W., Zipes, D. P. (2001). Sudden Cardiac Death, Genes, and Arrhythmogenesis : Consideration of New Population and Mechanistic Approaches From a National Heart, Lung, and Blood Institute Workshop, Part I. Circulation 103: 2361-2364 [Abstract] [Full Text]  
• McConnell, B. K., Fatkin, D., Semsarian, C., Jones, K. A., Georgakopoulos, D., Maguire, C. T., Healey, M. J., Mudd, J. O., Moskowitz, I. P. G., Conner, D. A., Giewat, M., Wakimoto, H., Berul, C. I., Schoen, F. J., Kass, D. A., Seidman, C. E., Seidman, J. G. (2001). Comparison of Two Murine Models of Familial Hypertrophic Cardiomyopathy. Circ. Res. 88: 383-389 [Abstract] [Full Text]  
• MOOLMAN-SMOOK, J., DE LANGE, W., CORFIELD, V., BRINK, P. (2000). Expression of HCM causing mutations: lessons learnt from genotype-phenotype studies of the South African founder MYH7 A797T mutation. J. Med. Genet. 37: 951-956 [Full Text]  
• Ho, C. Y., Lever, H. M., DeSanctis, R., Farver, C. F., Seidman, J. G., Seidman, C. E. (2000). Homozygous Mutation in Cardiac Troponin T : Implications for Hypertrophic Cardiomyopathy. Circulation 102: 1950-1955 [Abstract] [Full Text]  
• Nagueh, S. F., Kopelen, H. A., Lim, D.-S., Zoghbi, W. A., Quinones, M. A., Roberts, R., Marian, A. J. (2000). Tissue Doppler Imaging Consistently Detects Myocardial Contraction and Relaxation Abnormalities, Irrespective of Cardiac Hypertrophy, in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy. Circulation 102: 1346-1350 [Abstract] [Full Text]  
• Kokado, H., Shimizu, M., Yoshio, H., Ino, H., Okeie, K., Emoto, Y., Matsuyama, T., Yamaguchi, M., Yasuda, T., Fujino, N., Ito, H., Mabuchi, H. (2000). Clinical Features of Hypertrophic Cardiomyopathy Caused by a Lys183 Deletion Mutation in the Cardiac Troponin I Gene. Circulation 102: 663-669 [Abstract] [Full Text]  
• Spirito, P., Bellone, P., Harris, K. M., Bernabo, P., Bruzzi, P., Maron, B. J. (2000). Magnitude of Left Ventricular Hypertrophy and Risk of Sudden Death in Hypertrophic Cardiomyopathy. NEJM 342: 1778-1785 [Abstract] [Full Text]  
• Moolman, J. A., Reith, S., Uhl, K., Bailey, S., Gautel, M., Jeschke, B., Fischer, C., Ochs, J., McKenna, W. J., Klues, H., Vosberg, H.-P. (2000). A Newly Created Splice Donor Site in Exon 25 of the MyBP-C Gene Is Responsible for Inherited Hypertrophic Cardiomyopathy With Incomplete Disease Penetrance. Circulation 101: 1396-1402 [Abstract] [Full Text]  
• Watkins, H. (2000). Sudden Death in Hypertrophic Cardiomyopathy. NEJM 342: 422-424 [Full Text]  
• Winegrad, S. (2000). Myosin Binding Protein C, a Potential Regulator of Cardiac Contractility. Circ. Res. 86: 6-7 [Full Text]  
• Kunst, G., Kress, K. R., Gruen, M., Uttenweiler, D., Gautel, M., Fink, R. H. A. (2000). Myosin Binding Protein C, a Phosphorylation-Dependent Force Regulator in Muscle That Controls the Attachment of Myosin Heads by Its Interaction With Myosin S2. Circ. Res. 86: 51-58 [Abstract] [Full Text]  
• Sorajja, P., Elliott, P.M., Mckenna, W.J. (2000). The molecular genetics of hypertrophic cardiomyopathy: prognostic implications. Europace 2: 4-14  
• Elliott, P. M., D'Cruz, L., McKenna, W. J. (1999). Late-Onset Hypertrophic Cardiomyopathy Caused by a Mutation in the Cardiac Troponin T Gene. NEJM 341: 1855-1856 [Full Text]  
• Yang, Q., Sanbe, A., Osinska, H., Hewett, T. E., Klevitsky, R., Robbins, J. (1999). In Vivo Modeling of Myosin Binding Protein C Familial Hypertrophic Cardiomyopathy. Circ. Res. 85: 841-847 [Abstract] [Full Text]  
• Greenberg, H. M., Aretz, H. T. (1999). Case 31-1999- A 33-Year-Old Man with Wide-Complex Tachycardia and a Left Ventricular Mass. NEJM 341: 1217-1224 [Full Text]  
• Tobacman, L. S., Lin, D., Butters, C., Landis, C., Back, N., Pavlov, D., Homsher, E. (1999). Functional Consequences of Troponin T Mutations Found in Hypertrophic Cardiomyopathy. J. Biol. Chem. 274: 28363-28370 [Abstract] [Full Text]  
• Redwood, C. S., Moolman-Smook, J. C., Watkins, H. (1999). Properties of mutant contractile proteins that cause hypertrophic cardiomyopathy. Cardiovasc Res 44: 20-36 [Abstract] [Full Text]  
• Doi, Y. L., Kitaoka, H., Hitomi, N., Satoh, M., Kimura, A., Charron, P., Bennaceur, M., Isnard, R., Komajda, M., Carrier, L., Bonne, G., Schwartz, K., Camproux, A.-C., Richard, P., Hainque, B., Dubourg, O., Desnos, M., Hagege, A., Langlard, J. M., Bouhour, J.-B. (1999). Clinical Expression in Patients With Hypertrophic Cardiomyopathy Caused by Cardiac Myosin-Binding Protein C Gene Mutation • Response. Circulation 100 : 446-449 [Full Text]  
• Winegrad, S. (1999). Cardiac Myosin Binding Protein C. Circ. Res. 84: 1117-1126 [Abstract] [Full Text]  
• Maron, B. J., Mathenge, R., Casey, S. A., Poliac, L. C., Longe, T. F. (1999). Clinical profile of hypertrophic cardiomyopathy identified de novo in rural communities. J Am Coll Cardiol 33: 1590-1595 [Abstract] [Full Text]  
• Spirito, P., Rapezzi, C., Bellone, P., Betocchi, S., Autore, C., Conte, M. R., Bezante, G. P., Bruzzi, P. (1999). Infective Endocarditis in Hypertrophic Cardiomyopathy : Prevalence, Incidence, and Indications for Antibiotic Prophylaxis. Circulation 99: 2132-2137 [Abstract] [Full Text]