Noncompaction cardiomyopathy genetics: Difference between revisions
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==Overview== | ==Overview== | ||
Noncompaction cardiomyopathy | Noncompaction cardiomyopathy can appear sporadically or can be familial. Although mutations responsible for the sporadic cases have not been identified, several mutations that appear responsible for the familial transmission have been identified<ref>Zambrano E, Marshalko SJ, Jaffe CC, et al. Isolated noncompaction of the ventricular myocardium: clinical and molecular aspects of a rare cardiomyopathy. Lab Invest. 2002; 82: 117–122.</ref> . 18% <ref>Oechslin EN, Attenhofer Jost CH, Rojas JR, et al. Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol. 2000; 36: 493–500.</ref> to 50%<ref>Chin TK, Perloff JK, Williams RG, et al. Isolated noncompaction of left ventricular myocardium: a study of eight cases. Circulation. 1990; 82: 507–513.</ref> of family members are affected. There is predominantly an [[autosomal dominant]] mode of inheritance. There are more males with NCC than females which suggests a [[X linked pattern]] of inheritance in some patients. Noncompaction of ventricular myocardium was recently included in the 2006 classification of [[cardiomyopathy|cardiomyopathies]] as a genetic cardiomyopathy <ref name= AHA>{{Cite journal | last =Maron| first =Barry. | last2 =Towbin | first2 =Jeffrey. | last3 =Thiene| first3 =Gaetano | last4 =Antzelevitch| first4 =Charles | last5 =Corrado| first5 =Domenico. | title = Contemporary Definitions and Classification of the Cardiomyopathies | journal = American Heart Association Journals | publisher = American Heart Association t | volume = 113 | issue =14 | pages =| year =2006 | url= http://circ.ahajournals.org/cgi/content/full/113/14/1807| format = webpage | id = 113:1807-1816}}</ref>. | ||
== | ==Patterns of Inheritance== | ||
The majority of the time the pattern of inheritance is [[autosomal dominant]]. In some families, the mode of transmission appears to be [[x-linked]]<ref>Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-linked noncompaction of the ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997; 72:257–265.</ref> or via mitochondrial transmission. | |||
==Genes Involved== | |||
Several potential genetic abnormalities have been identified: | Several potential genetic abnormalities have been identified: | ||
* | *The gene that encodes for [[alpha-dystrobrevin]]<ref>Ichida F, Tsubata S, Bowles KR, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation. 2001; 103: 1256–1263.</ref>. This is a [[dystrophin-associated protein]] which has been mapped to [[chromosome 18q12]]. The role of this protein is to preserve the structural integrity of the muscle membrane. | ||
* | *An X-linked genetic defect which involves a mutation in the gene G4.5 (TAZ) of the Xq28 chromosome region (a gene which encodes for [[tafazzin]]), the same region of the chromosome involved in several [[myopathies]] with cardiac involvement are located. These include [[Barth syndrome]]<ref>Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-linked noncompaction of the ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997; 72:257–265.</ref>, [[Emery-Dreifuss muscular dystrophy]], and [[myotubular myopathy]]. As a result, some patients with NCC may have features of [[Barth syndrome]]. | ||
* Mutations of the [[ryanodine receptor 2 gene]] ([[RyR2]]) as has been seen in patients with [[arrhythmogenic right | * Mutations of the [[ryanodine receptor 2 gene]] ([[RyR2]]) as has been seen in patients with [[arrhythmogenic right ventricular dysplasia]]. | ||
* Deletions of the [[FKBP12 gene]] result in noncompaction in the mouse. | * Deletions of the [[FKBP12 gene]] result in noncompaction in the mouse<ref>Rigopoulos A, Rizos IK, Aggeli C, et al. Isolated left ventricular noncompaction: an unclassified cardiomyopathy with severe prognosis in adults. Cardiology. 2002;98:25–32.</ref>. | ||
*Knockout of the [[Peg1]] gene has been associated with NCC in the mouse <ref>Rigopoulos A, Rizos IK, Aggeli C, et al. Isolated left ventricular noncompaction: an unclassified cardiomyopathy with severe prognosis in adults. Cardiology. 2002; 98: 25–32.</ref>. | |||
* [[LMNA]] mutations | * [[LMNA]] mutations | ||
*Abnormalities of | *Abnormalities of transcription factors such as [[NKX2.5]] and [[TBX5]]. | ||
*Abnormalities of 11p15 as suggested in a GWAS analysis. | *Abnormalities of 11p15 as suggested in a [[GWAS]] analysis. | ||
*22q11 deletion | *22q11 deletion | ||
*Distal 5q deletion involving the [[CSX]] gene <ref>Pauli RM, Scheib-Wixted S, Cripe L, et al. Ventricular noncompaction and distal chromosome 5q deletion. Am J Med Genet. 1999;85:419–423.</ref> | |||
==References== | ==References== | ||
Latest revision as of 14:38, 6 August 2011
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Noncompaction Cardiomyopathy Microchapters |
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Pathophysiology |
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Differentiating Noncompaction Cardiomyopathy from other Diseases |
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Noncompaction cardiomyopathy genetics On the Web |
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Risk calculators and risk factors for Noncompaction cardiomyopathy genetics |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Noncompaction cardiomyopathy can appear sporadically or can be familial. Although mutations responsible for the sporadic cases have not been identified, several mutations that appear responsible for the familial transmission have been identified[1] . 18% [2] to 50%[3] of family members are affected. There is predominantly an autosomal dominant mode of inheritance. There are more males with NCC than females which suggests a X linked pattern of inheritance in some patients. Noncompaction of ventricular myocardium was recently included in the 2006 classification of cardiomyopathies as a genetic cardiomyopathy [4].
Patterns of Inheritance
The majority of the time the pattern of inheritance is autosomal dominant. In some families, the mode of transmission appears to be x-linked[5] or via mitochondrial transmission.
Genes Involved
Several potential genetic abnormalities have been identified:
- The gene that encodes for alpha-dystrobrevin[6]. This is a dystrophin-associated protein which has been mapped to chromosome 18q12. The role of this protein is to preserve the structural integrity of the muscle membrane.
- An X-linked genetic defect which involves a mutation in the gene G4.5 (TAZ) of the Xq28 chromosome region (a gene which encodes for tafazzin), the same region of the chromosome involved in several myopathies with cardiac involvement are located. These include Barth syndrome[7], Emery-Dreifuss muscular dystrophy, and myotubular myopathy. As a result, some patients with NCC may have features of Barth syndrome.
- Mutations of the ryanodine receptor 2 gene (RyR2) as has been seen in patients with arrhythmogenic right ventricular dysplasia.
- Deletions of the FKBP12 gene result in noncompaction in the mouse[8].
- Knockout of the Peg1 gene has been associated with NCC in the mouse [9].
- LMNA mutations
- Abnormalities of transcription factors such as NKX2.5 and TBX5.
- Abnormalities of 11p15 as suggested in a GWAS analysis.
- 22q11 deletion
- Distal 5q deletion involving the CSX gene [10]
References
- ↑ Zambrano E, Marshalko SJ, Jaffe CC, et al. Isolated noncompaction of the ventricular myocardium: clinical and molecular aspects of a rare cardiomyopathy. Lab Invest. 2002; 82: 117–122.
- ↑ Oechslin EN, Attenhofer Jost CH, Rojas JR, et al. Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol. 2000; 36: 493–500.
- ↑ Chin TK, Perloff JK, Williams RG, et al. Isolated noncompaction of left ventricular myocardium: a study of eight cases. Circulation. 1990; 82: 507–513.
- ↑ Maron, Barry.; Towbin, Jeffrey.; Thiene, Gaetano; Antzelevitch, Charles; Corrado, Domenico. (2006). "Contemporary Definitions and Classification of the Cardiomyopathies" (webpage). American Heart Association Journals. American Heart Association t. 113 (14). 113:1807-1816.
- ↑ Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-linked noncompaction of the ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997; 72:257–265.
- ↑ Ichida F, Tsubata S, Bowles KR, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation. 2001; 103: 1256–1263.
- ↑ Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-linked noncompaction of the ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997; 72:257–265.
- ↑ Rigopoulos A, Rizos IK, Aggeli C, et al. Isolated left ventricular noncompaction: an unclassified cardiomyopathy with severe prognosis in adults. Cardiology. 2002;98:25–32.
- ↑ Rigopoulos A, Rizos IK, Aggeli C, et al. Isolated left ventricular noncompaction: an unclassified cardiomyopathy with severe prognosis in adults. Cardiology. 2002; 98: 25–32.
- ↑ Pauli RM, Scheib-Wixted S, Cripe L, et al. Ventricular noncompaction and distal chromosome 5q deletion. Am J Med Genet. 1999;85:419–423.