Dilated cardiomyopathy pathophysiology: Difference between revisions

Jump to navigation Jump to search
Line 39: Line 39:
|-
|-
| [[BCL2-associated athanogene 3]] || [[BAG3]] ||
| [[BCL2-associated athanogene 3]] || [[BAG3]] ||
<ref name="pmid21353195">{{cite journal| author=Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Züchner S et al.| title=Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy. | journal=Am J Hum Genet | year= 2011 | volume= 88 | issue= 3 | pages= 273-82 | pmid=21353195 | doi=10.1016/j.ajhg.2011.01.016 | pmc=PMC3059419 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21353195 }} </ref>
|-
|-
| [[Cardiotropin]] || [[CTF1]] ||
| [[Cardiotropin]] || [[CTF1]] ||
|-
|-
| [[Cysteine and glycine-rich protein 3]] || [[CSRP3]] ||
| [[Cysteine and glycine-rich protein 3]] || [[CSRP3]] ||
<ref name="pmid14567970">{{cite journal| author=Mohapatra B, Jimenez S, Lin JH, Bowles KR, Coveler KJ, Marx JG et al.| title=Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis. | journal=Mol Genet Metab | year= 2003 | volume= 80 | issue= 1-2 | pages= 207-15 | pmid=14567970 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14567970 }} </ref>
|-
|-
| [[Desmin]] || [[DES]] ||
| [[Desmin]] || [[DES]] ||

Revision as of 18:08, 11 October 2013

Dilated cardiomyopathy Microchapters

Home

Patient Information

Overview

Historical Perspective

Pathophysiology

Classification

Causes

Differentiating Dilated cardiomyopathy from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Dilated cardiomyopathy pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Dilated cardiomyopathy pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Dilated cardiomyopathy pathophysiology

CDC on Dilated cardiomyopathy pathophysiology

Dilated cardiomyopathy pathophysiology in the news

Blogs on Dilated cardiomyopathy pathophysiology

Directions to Hospitals Treating Dilated cardiomyopathy

Risk calculators and risk factors for Dilated cardiomyopathy pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sachin Shah, M.D., Jennifer Hall

Overview

Cardiomyopathies are defined as a heterogeneous group of diseases of the heart associated with a mechanical and/or electrical dysfunction that usually (but not always) exhibit inappropropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic.[1] Phenotypic characteristics typically include ventricular chamber enlargement and systolic dysfunction with normal wall thickness.[1] Patients with dilated cardiomyopathy may experience a progressive decline in left ventricular contractile function, ventricular and supraventricular arrhythmias, conduction system problems, thromboembolism, sudden cardiac death and/or heart failure.[1] Dilated cardiomyopathy is the third most common cause of heart failure.[1]

Pathophysiology

Genetics

Our understanding of the role of genetics in dilated cardiomyopathy continues to grow. Inherited familial dilated cardiomyopathy has been associated with 50 mutations in genes encoding cytoskeletal, nucleoskeletal, mitochondrial and calcium handling proteins.[2] These mutations are listed below.

Genes Encoding Plasma Membrane Proteins

Gene Abbreviation References
Laminin alpha 4 LAMA4 [3]
Sarcoglycan delta SGCD [4][5]

Genes Encoding Cytoskeletal Proteins

Gene Abbreviation References
Actin, alpha, cardiac muscle 1 ACTC1 [6]
Actinin, alpha 2 ACTN2 [7]
Ankyrin repeat domain 1 ANKRD1

[8]

BCL2-associated athanogene 3 BAG3

[9]

Cardiotropin CTF1
Cysteine and glycine-rich protein 3 CSRP3

[7]

Desmin DES
Desmocollin 2 DSC2
Desmoplakin DSP

[10][11][12]

DNAJ (Hsp40) homology, subfamily C, member 19 DNAJC19
Dystrophin DMD
Eyes absent homology 4 EYA4
Four and a half LIM domains 2 FHL2
Fukutin FKTN
Lysosomal-associated membrane protein 2 LAMP2
LIM domain binding 3 LDB3
Myosin binding protein C, cardiac MYBPC3
Myosin, heavy chain 6, cardiac muscle, alpha MYH6
Myosin, heavy chain 7, cardiac muscle, alpha MYH7
Nexilin (F actin binding protein) NEXN
Presenilin 1 PSEN1
Presenilin 2 PSEN2
RNA binding motif protein 20 RBM20
Sarcoglycan alpha SGCD
Sodium channel, volatage-gated, type V, alpha subunit SCN5A
Tafazzin TAZ
Titin-cap TCAP
Thymopoietin TMPO
Troponin C type 1 (slow) TNNC1
Troponin I type 3 (cardiac) TNNI3
Troponin T type 2 (cardiac) TNNT2
Tropomyosin 1 (alpha) TPM1
Titin TTN
Vinculin VCL

Genes Encoding Calcium Handling Proteins

Gene Abbreviation References
Phospholamban PLN

Genes Encoding Mitochondrial Proteins

Gene Abbreviation References
Succinate dehydrogenase complex, subunit A, flavoprotein SDHA

Genes Encoding Nuclear Proteins

Gene Abbreviation References
ATP-binding cassette, sub-family C, member 9 ABCC9
Emerin EMD
Forkhead box D4 FOXD4
Lamin A/C LMNA
Spectrin repeat containing, nuclear envelope 1 SYNE1
Spectrin repeat containing, nuclear envelope 2 SYNE2

The increase in whole exome and whole genome sequencing has significantly increased the number of rare variants that are associated with dilated cardiomyopathy [2]. A challenge in the field today is that many individuals without disease carry rare variants in their genome. Thus the task at hand is not in the sequencing but rather in the translation to define if the rare variants discovered are in fact pathophysiologic in nature. Secondly, evidence is accumulating that many patients with dilated cardiomyopathy may have many different mutations that contribute to or modify disease. [13]

Genetic Testing

Associated Conditions

A review of systems is also helpful in regards to connective tissue disease associated dilated cardiomyopathy. Some of the disease that can be associated with dilated cardiomyopathy are:

Gross Pathology

Images shown below are Courtesy of Professor Peter Anderson DVM PhD and published with permission. © PEIR, University of Alabama at Birmingham, Department of Pathology

References

  1. 1.0 1.1 1.2 1.3 Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D; 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 Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention". Circulation. 113 (14): 1807–16. doi:10.1161/CIRCULATIONAHA.106.174287. PMID 16567565.
  2. 2.0 2.1 McNally EM, Golbus JR, Puckelwartz MJ (2013). "Genetic mutations and mechanisms in dilated cardiomyopathy". J Clin Invest. 123 (1): 19–26. doi:10.1172/JCI62862. PMC 3533274. PMID 23281406.
  3. Knöll R, Postel R, Wang J, Krätzner R, Hennecke G, Vacaru AM; et al. (2007). "Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells". Circulation. 116 (5): 515–25. doi:10.1161/CIRCULATIONAHA.107.689984. PMID 17646580.
  4. {{cite journal| author=Tsubata S, Bowles KR, Vatta M, Zintz C, Titus J, Muhonen L et al.| title=Mutations in the human delta-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. | journal=J Clin Invest | year= 2000 | volume= 106 | issue= 5 | pages= 655-62 | pmid=10974018 | doi=10.1172/JCI9224 | pmc=PMC381284 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10974018
  5. Trabelsi M, Kavian N, Daoud F, Commere V, Deburgrave N, Beugnet C; et al. (2008). "Revised spectrum of mutations in sarcoglycanopathies". Eur J Hum Genet. 16 (7): 793–803. doi:10.1038/ejhg.2008.9. PMID 18285821.
  6. Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT (1998). "Actin mutations in dilated cardiomyopathy, a heritable form of heart failure". Science. 280 (5364): 750–2. PMID 9563954.
  7. 7.0 7.1 Mohapatra B, Jimenez S, Lin JH, Bowles KR, Coveler KJ, Marx JG; et al. (2003). "Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis". Mol Genet Metab. 80 (1–2): 207–15. PMID 14567970.
  8. Duboscq-Bidot L, Charron P, Ruppert V, Fauchier L, Richter A, Tavazzi L; et al. (2009). "Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy". Eur Heart J. 30 (17): 2128–36. doi:10.1093/eurheartj/ehp225. PMID 19525294.
  9. Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Züchner S; et al. (2011). "Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy". Am J Hum Genet. 88 (3): 273–82. doi:10.1016/j.ajhg.2011.01.016. PMC 3059419. PMID 21353195.
  10. Norgett EE, Hatsell SJ, Carvajal-Huerta L, Cabezas JC, Common J, Purkis PE; et al. (2000). "Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma". Hum Mol Genet. 9 (18): 2761–6. PMID 11063735.
  11. Uzumcu A, Norgett EE, Dindar A, Uyguner O, Nisli K, Kayserili H; et al. (2006). "Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome". J Med Genet. 43 (2): e5. doi:10.1136/jmg.2005.032904. PMC 2564645. PMID 16467215.
  12. Rasmussen TB, Hansen J, Nissen PH, Palmfeldt J, Dalager S, Jensen UB; et al. (2013). "Protein expression studies of desmoplakin mutations in cardiomyopathy patients reveal different molecular disease mechanisms". Clin Genet. 84 (1): 20–30. doi:10.1111/cge.12056. PMID 23137101.
  13. Golbus JR, Puckelwartz MJ, Fahrenbach JP, Dellefave-Castillo LM, Wolfgeher D, McNally EM (2012). "Population-based variation in cardiomyopathy genes". Circ Cardiovasc Genet. 5 (4): 391–9. doi:10.1161/CIRCGENETICS.112.962928. PMC 3495587. PMID 22763267.


Template:WikiDoc Sources