Genetics of Cardiovascular and Neuromuscular Disease

NCT00138931 | Recruiting

• 1 other identifier: 8249
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiomyopathy; Arrhythmia; Muscular Dystrophy

Keywords

Cardiomyopathy; Arrhythmia; Muscular Dystrophy

Outcome Measures

Primary Outcomes (1)

• Identification of genetic causes of cardiomyopathy

  unlimited

Interventions

Blood draw (genetic testing) PROCEDURE

Blood draw (genetic testing)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Related Publications (39)

• Noguchi S, McNally EM, Ben Othmane K, Hagiwara Y, Mizuno Y, Yoshida M, Yamamoto H, Bonnemann 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. doi: 10.1126/science.270.5237.819.

  PMID: 7481775 BACKGROUND

• McNally EM, Duggan D, Gorospe JR, Bonnemann 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. doi: 10.1093/hmg/5.11.1841.

  PMID: 8923014 BACKGROUND

• McNally EM, Passos-Bueno MR, Bonnemann CG, Vainzof M, de Sa 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.

  PMID: 8900232 BACKGROUND

• 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.

  PMID: 9106535 BACKGROUND

• 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. doi: 10.1086/514896.

  PMID: 9382102 BACKGROUND

• 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. doi: 10.1093/hmg/9.2.217.

  PMID: 10607832 BACKGROUND

• 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. doi: 10.1016/s0960-8966(99)00063-2.

  PMID: 10714584 BACKGROUND

• 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. doi: 10.1002/(sici)1096-8628(20000410)91:43.0.co;2-s.

  PMID: 10766988 BACKGROUND

• 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. doi: 10.1002/1096-8628(2001)9999:99993.0.co;2-o.

  PMID: 11251997 BACKGROUND

• Vainzof M, Anderson LV, McNally EM, Davis DB, Faulkner G, Valle G, Moreira ES, Pavanello RC, Passos-Bueno MR, Zatz M. Dysferlin protein analysis in limb-girdle muscular dystrophies. J Mol Neurosci. 2001 Aug;17(1):71-80. doi: 10.1385/JMN:17:1:71.

  PMID: 11665864 BACKGROUND

• McNally EM. Beta-myosin heavy chain gene mutations in familial hypertrophic cardiomyopathy: the usual suspect? Circ Res. 2002 Feb 22;90(3):246-7. No abstract available.

  PMID: 11861410 BACKGROUND

• 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. doi: 10.1093/hmg/11.18.2147.

  PMID: 12189167 BACKGROUND

• McNally E, Allikian M, Wheeler MT, Mislow JM, Heydemann A. Cytoskeletal defects in cardiomyopathy. J Mol Cell Cardiol. 2003 Mar;35(3):231-41. doi: 10.1016/s0022-2828(03)00018-x.

  PMID: 12676538 BACKGROUND

• 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. doi: 10.1186/1471-2350-4-4.

  PMID: 12854972 BACKGROUND

• 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. doi: 10.1016/j.yexcr.2003.07.002.

  PMID: 14644157 BACKGROUND

• McNally EM, Towbin JA. Cardiomyopathy in muscular dystrophy workshop. 28-30 September 2003, Tucson, Arizona. Neuromuscul Disord. 2004 Jul;14(7):442-8. doi: 10.1016/j.nmd.2004.04.003. No abstract available.

  PMID: 15266661 BACKGROUND

• 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. doi: 10.1016/j.jacc.2006.07.016. Epub 2006 Sep 12.

  PMID: 17010801 BACKGROUND

• Heydemann A, Doherty KR, McNally EM. Genetic modifiers of muscular dystrophy: implications for therapy. Biochim Biophys Acta. 2007 Feb;1772(2):216-28. doi: 10.1016/j.bbadis.2006.06.013. Epub 2006 Jul 11.

  PMID: 16916601 BACKGROUND

• 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. doi: 10.1093/hmg/ddl453. Epub 2006 Dec 12.

  PMID: 17164264 BACKGROUND

• McNally EM. New approaches in the therapy of cardiomyopathy in muscular dystrophy. Annu Rev Med. 2007;58:75-88. doi: 10.1146/annurev.med.58.011706.144703.

  PMID: 17217326 BACKGROUND

• Allikian MJ, McNally EM. Processing and assembly of the dystrophin glycoprotein complex. Traffic. 2007 Mar;8(3):177-83. doi: 10.1111/j.1600-0854.2006.00519.x. Epub 2007 Jan 26.

  PMID: 17274800 BACKGROUND

• 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. doi: 10.1016/j.tcm.2006.12.002.

  PMID: 17292047 BACKGROUND

• McNally EM, Pytel P. Muscle diseases: the muscular dystrophies. Annu Rev Pathol. 2007;2:87-109. doi: 10.1146/annurev.pathol.2.010506.091936.

  PMID: 18039094 BACKGROUND

• 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. No abstract available.

  PMID: 18519860 BACKGROUND

• 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.

  PMID: 18791812 BACKGROUND

• 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.

  PMID: 19944109 BACKGROUND

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

  PMID: 20186049 BACKGROUND

• 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.

  PMID: 20857240 BACKGROUND

• 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.

  PMID: 20959497 BACKGROUND

• 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. No abstract available.

  PMID: 21406661 BACKGROUND

• 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.

  PMID: 21621072 BACKGROUND

• 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.

  PMID: 21642660 BACKGROUND

• Puckelwartz MJ, Depreux FF, McNally EM. Gene expression, chromosome position and lamin A/C mutations. Nucleus. 2011 May-Jun;2(3):162-7. doi: 10.4161/nucl.2.3.16003.

  PMID: 21818408 BACKGROUND

• 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.

  PMID: 22763267 BACKGROUND

• 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.

  PMID: 23440719 BACKGROUND

• 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. doi: 10.1016/j.nmd.2007.01.005. Epub 2007 Mar 1.

  PMID: 17336067 RESULT

• 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.

  PMID: 20117437 RESULT

• 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.

  PMID: 24526712 RESULT

• 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.

  PMID: 20031619 DERIVED

MeSH Terms

Conditions

Cardiomyopathies; Arrhythmias, Cardiac; Muscular Dystrophies

Interventions

Blood Specimen Collection; Genetic Testing

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Elizabeth McNally, MD PhD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Dellefave, MS

CONTACT

773-702-4310; Ldellefa@medicine.bsd.uchicago.edu

Elizabeth McNally, MD PhD

CONTACT

773-702-2679; emcnally@uchicago.edu

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2005
• First Posted: August 30, 2005
• Study Start: September 1, 1996
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: September 9, 2025

Record last verified: 2025-09

Locations

US (1)