Genetics of Cardiovascular and Neuromuscular Disease

This study is currently recruiting participants. (see Contacts and Locations)

Verified October 2014 by University of Chicago

Sponsor:

Information provided by (Responsible Party):

University of Chicago

ClinicalTrials.gov Identifier:

NCT00138931

First received: August 29, 2005

Last updated: October 6, 2014

Last verified: October 2014

History of Changes

Purpose

We are studying the genetics of human cardiovascular and neuromuscular disease. There are many different genetic regions that have been associated with the development of cardiomyopathy. An equal number of genetic regions have been associated with muscular dystrophy and there is overlap because some of the identical genes, when mutated, produce both cardiomyopathy and muscular dystrophy. We are working to identify genes and gene mutations associated with cardiomyopathy, arrhythmias and muscular dystrophy. We propose to screen these samples for mutations in genes known to be involved in these disorders.

Condition	Intervention
Cardiomyopathy Arrhythmia Muscular Dystrophy	Procedure: Blood draw (genetic testing)


Study Type:	Observational
Study Design:	Observational Model: Family-Based
Official Title:	Genetic Studies of Patients and Their Families With Inherited Cardiovascular and Neuromuscular Diseases.

Resource links provided by NLM:

MedlinePlus related topics: Cardiomyopathy Genetic Testing Muscular Dystrophy Neuromuscular Disorders

Genetic and Rare Diseases Information Center resources: Muscular Dystrophy

U.S. FDA Resources

Further study details as provided by University of Chicago:

Primary Outcome Measures:

Identification of genetic causes of cardiomyopathy [ Time Frame: unlimited ] [ Designated as safety issue: No ]


Estimated Enrollment:	2000
Study Start Date:	September 1996
Estimated Primary Completion Date:	January 2025 (Final data collection date for primary outcome measure)

Intervention Details:

genetic testing

Blood draw (genetic testing)

Eligibility


Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Patients of all ages with familial idiopathic cardiomyopathy, including dilated, hypertrophic, and left ventricular non-compaction cardiomyopathy

Criteria

Inclusion Criteria:

Patients of all ages will be considered for the study. In particular, families with more than one affected relative will be sought.

Exclusion Criteria:

Subjects without a suspected inherited cardiovascular or neuromuscular disorder will be excluded from this study.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00138931

Contacts


Contact: Lisa Dellefave, MS	773-702-4310	Ldellefa@medicine.bsd.uchicago.edu
Contact: Elizabeth McNally, MD PhD	773-702-2679	emcnally@uchicago.edu

Locations


United States, Illinois
University of Chicago	Recruiting
Chicago, Illinois, United States, 60637
Contact: Lisa Dellefave, MS 773-702-4310 Ldellefa@medicine.bsd.uchicago.edu

Sponsors and Collaborators

University of Chicago

Investigators


Principal Investigator:	Elizabeth McNally, MD PhD	University of Chicago

More Information

Additional Information:

McNally Lab Homepage This link exits the ClinicalTrials.gov site

Publications:

MacLeod H, Pytel P, Wollmann R, Chelmicka-Schorr E, Silver K, Anderson RB, Waggoner D, McNally EM. A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex. Neuromuscul Disord. 2007 Apr;17(4):285-9. Epub 2007 Mar 1.

Lakdawala NK, Dellefave L, Redwood CS, Sparks E, Cirino AL, Depalma S, Colan SD, Funke B, Zimmerman RS, Robinson P, Watkins H, Seidman CE, Seidman JG, McNally EM, Ho CY. Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy. J Am Coll Cardiol. 2010 Jan 26;55(4):320-9. doi: 10.1016/j.jacc.2009.11.017.

Puckelwartz MJ, Pesce LL, Nelakuditi V, Dellefave-Castillo L, Golbus JR, Day SM, Cappola TP, Dorn GW 2nd, Foster IT, McNally EM. Supercomputing for the parallelization of whole genome analysis. Bioinformatics. 2014 Jun 1;30(11):1508-13. doi: 10.1093/bioinformatics/btu071. Epub 2014 Feb 12.

Noguchi S, McNally EM, Ben Othmane K, Hagiwara Y, Mizuno Y, Yoshida M, Yamamoto H, Bönnemann CG, Gussoni E, Denton PH, Kyriakides T, Middleton L, Hentati F, Ben Hamida M, Nonaka I, Vance JM, Kunkel LM, Ozawa E. Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy. Science. 1995 Nov 3;270(5237):819-22.

McNally EM, Duggan D, Gorospe JR, Bönnemann CG, Fanin M, Pegoraro E, Lidov HG, Noguchi S, Ozawa E, Finkel RS, Cruse RP, Angelini C, Kunkel LM, Hoffman EP. Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy. Hum Mol Genet. 1996 Nov;5(11):1841-7.

McNally EM, Passos-Bueno MR, Bönnemann CG, Vainzof M, de Sá Moreira E, Lidov HG, Othmane KB, Denton PH, Vance JM, Zatz M, Kunkel LM. Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation. Am J Hum Genet. 1996 Nov;59(5):1040-7.

van der Kooi AJ, van Meegen M, Ledderhof TM, McNally EM, de Visser M, Bolhuis PA. Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11-21. Am J Hum Genet. 1997 Apr;60(4):891-5.

Messina DN, Speer MC, Pericak-Vance MA, McNally EM. Linkage of familial dilated cardiomyopathy with conduction defect and muscular dystrophy to chromosome 6q23. Am J Hum Genet. 1997 Oct;61(4):909-17.

Davis DB, Delmonte AJ, Ly CT, McNally EM. Myoferlin, a candidate gene and potential modifier of muscular dystrophy. Hum Mol Genet. 2000 Jan 22;9(2):217-26.

Nowak KJ, Walsh P, Jacob RL, Johnsen RD, Peverall J, McNally EM, Wilton SD, Kakulas BA, Laing NG. Severe gamma-sarcoglycanopathy caused by a novel missense mutation and a large deletion. Neuromuscul Disord. 2000 Feb;10(2):100-7.

McNally EM, Ly CT, Rosenmann H, Mitrani Rosenbaum S, Jiang W, Anderson LV, Soffer D, Argov Z. Splicing mutation in dysferlin produces limb-girdle muscular dystrophy with inflammation. Am J Med Genet. 2000 Apr 10;91(4):305-12.

de Paula F, Vainzof M, Bernardino AL, McNally E, Kunkel LM, Zatz M. Mutations in the caveolin-3 gene: When are they pathogenic? Am J Med Genet. 2001 Apr 1;99(4):303-7.

Vainzof, M., L. V.B. Anderson, E. M. McNally, D. B. Davis, G. Faulkner, E. S. Moreira, R. C. M. Pavanello, M. R. Passos-Bueno and M. Zatz. Dysferlin protein analysis in the muscular dystrophies. (2001) J. Mol. Neurosci. 1:71-80.

McNally EM. Beta-myosin heavy chain gene mutations in familial hypertrophic cardiomyopathy: the usual suspect? Circ Res. 2002 Feb 22;90(3):246-7.

Wheeler MT, Zarnegar S, McNally EM. Zeta-sarcoglycan, a novel component of the sarcoglycan complex, is reduced in muscular dystrophy. Hum Mol Genet. 2002 Sep 1;11(18):2147-54.

McNally E, Allikian M, Wheeler MT, Mislow JM, Heydemann A. Cytoskeletal defects in cardiomyopathy. J Mol Cell Cardiol. 2003 Mar;35(3):231-41. Review.

MacLeod HM, Culley MR, Huber JM, McNally EM. Lamin A/C truncation in dilated cardiomyopathy with conduction disease. BMC Med Genet. 2003 Jul 10;4:4.

Muchir A, van Engelen BG, Lammens M, Mislow JM, McNally E, Schwartz K, Bonne G. Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene. Exp Cell Res. 2003 Dec 10;291(2):352-62.

McNally, E. M. and J. A. Towbin. Cardiomyopathy in Muscular Dystrophy. (2004) Neuromusc. Disorders 14:442-8.

DeWitt MM, MacLeod HM, Soliven B, McNally EM. Phospholamban R14 deletion results in late-onset, mild, hereditary dilated cardiomyopathy. J Am Coll Cardiol. 2006 Oct 3;48(7):1396-8. Epub 2006 Sep 12.

Heydemann A, Doherty KR, McNally EM. Genetic modifiers of muscular dystrophy: implications for therapy. Biochim Biophys Acta. 2007 Feb;1772(2):216-28. Epub 2006 Jul 11. Review.

Heydemann A, Demonbreun A, Hadhazy M, Earley JU, McNally EM. Nuclear sequestration of delta-sarcoglycan disrupts the nuclear localization of lamin A/C and emerin in cardiomyocytes. Hum Mol Genet. 2007 Feb 15;16(4):355-63. Epub 2006 Dec 12.

McNally EM. New approaches in the therapy of cardiomyopathy in muscular dystrophy. Annu Rev Med. 2007;58:75-88. Review.

Allikian MJ, McNally EM. Processing and assembly of the dystrophin glycoprotein complex. Traffic. 2007 Mar;8(3):177-83. Epub 2007 Jan 26. Review.

Heydemann A, McNally EM. Consequences of disrupting the dystrophin-sarcoglycan complex in cardiac and skeletal myopathy. Trends Cardiovasc Med. 2007 Feb;17(2):55-9. Review.

McNally EM, Pytel P. Muscle diseases: the muscular dystrophies. Annu Rev Pathol. 2007;2:87-109. Review.

Dellefave L, McNally EM. Sarcomere mutations in cardiomyopathy, noncompaction, and the developing heart. Circulation. 2008 Jun 3;117(22):2847-9. doi: 10.1161/CIRCULATIONAHA.108.781518. Review.

MacLeod HM, McNally EM. A pilot study of a family history risk assessment tool for cardiovascular disease. J Genet Couns. 2008 Oct;17(5):499-507. doi: 10.1007/s10897-008-9174-z. Epub 2008 Sep 13.

Puckelwartz MJ, Kessler EJ, Kim G, Dewitt MM, Zhang Y, Earley JU, Depreux FF, Holaska J, Mewborn SK, Pytel P, McNally EM. Nesprin-1 mutations in human and murine cardiomyopathy. J Mol Cell Cardiol. 2010 Apr;48(4):600-8. doi: 10.1016/j.yjmcc.2009.11.006. Epub 2009 Nov 24.

Dellefave L, McNally EM. The genetics of dilated cardiomyopathy. Curr Opin Cardiol. 2010 May;25(3):198-204. doi: 10.1097/HCO.0b013e328337ba52. Review.

Romfh A, McNally EM. Cardiac assessment in duchenne and becker muscular dystrophies. Curr Heart Fail Rep. 2010 Dec;7(4):212-8. doi: 10.1007/s11897-010-0028-2. Review.

Swaggart KA, Heydemann A, Palmer AA, McNally EM. Distinct genetic regions modify specific muscle groups in muscular dystrophy. Physiol Genomics. 2011 Jan 7;43(1):24-31. doi: 10.1152/physiolgenomics.00172.2010. Epub 2010 Oct 19.

McNally EM, Patel AR. Cardiac magnetic resonance of left ventricular trabeculation: the new normal. Circ Cardiovasc Imaging. 2011 Mar;4(2):84-6. doi: 10.1161/CIRCIMAGING.110.962472.

Posey AD Jr, Demonbreun A, McNally EM. Ferlin proteins in myoblast fusion and muscle growth. Curr Top Dev Biol. 2011;96:203-30. doi: 10.1016/B978-0-12-385940-2.00008-5. Review.

McNally EM, Sparano D. Mechanisms and management of the heart in myotonic dystrophy. Heart. 2011 Jul;97(13):1094-100. doi: 10.1136/hrt.2010.214197. Review.

Puckelwartz MJ, Depreux FF, McNally EM. Gene expression, chromosome position and lamin A/C mutations. Nucleus. 2011 May-Jun;2(3):162-7. doi: 10.1083/jcb.201101046.

Golbus JR, Puckelwartz MJ, Fahrenbach JP, Dellefave-Castillo LM, Wolfgeher D, McNally EM. Population-based variation in cardiomyopathy genes. Circ Cardiovasc Genet. 2012 Aug 1;5(4):391-9. doi: 10.1161/CIRCGENETICS.112.962928. Epub 2012 Jul 4. Erratum in: Circ Cardiovasc Genet. 2012 Oct 1;5(5):e48.

Flanigan KM, Ceco E, Lamar KM, Kaminoh Y, Dunn DM, Mendell JR, King WM, Pestronk A, Florence JM, Mathews KD, Finkel RS, Swoboda KJ, Gappmaier E, Howard MT, Day JW, McDonald C, McNally EM, Weiss RB; United Dystrophinopathy Project. LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy. Ann Neurol. 2013 Apr;73(4):481-8. doi: 10.1002/ana.23819. Epub 2013 Feb 20.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dellefave LM, Pytel P, Mewborn S, Mora B, Guris DL, Fedson S, Waggoner D, Moskowitz I, McNally EM. Sarcomere mutations in cardiomyopathy with left ventricular hypertrabeculation. Circ Cardiovasc Genet. 2009 Oct;2(5):442-9. doi: 10.1161/CIRCGENETICS.109.861955. Epub 2009 Jul 24.


Responsible Party:	University of Chicago
ClinicalTrials.gov Identifier:	NCT00138931 History of Changes
Other Study ID Numbers:	8249
Study First Received:	August 29, 2005
Last Updated:	October 6, 2014
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Chicago:


Cardiomyopathy Arrhythmia Muscular Dystrophy

Additional relevant MeSH terms:


Cardiomyopathies Muscular Dystrophies Neuromuscular Diseases Cardiovascular Diseases Genetic Diseases, Inborn	Heart Diseases Muscular Diseases Muscular Disorders, Atrophic Musculoskeletal Diseases Nervous System Diseases

ClinicalTrials.gov processed this record on March 02, 2015

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