Malignant and benign mutations in familial cardiomyopathies

Insights into mutations linked to complex cardiovascular phenotypes

Qian Xu, Shannamar Dewey, Susan Nguyen, Aldrin V Gomes

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Cardiomyopathies, familial or sporadic, have become recognized as one of the leading cardiac threats. Hypertrophic cardiomyopathy (HCM) affects 0.2% of the population and is the leading cause of sudden death in young adults. Dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM) are associated with sudden death as well as heart transplantations. Ventricular noncompaction cardiomyopathy (VNCM) is associated with heart failure and arrhythmias. Currently, more than 630 mutations in 10 sarcomeric genes associated with cardiomyopathy have been identified. HCM is associated with more than 550 mutations, whereas DCM, RCM and VNCM are associated with 52, 14 and 17 mutations, respectively. In many cases, the genes affected present a varying range of phenotypic and pathological severity. Recent data suggest that at least two main genetic determinants are involved in the pathogenesis and phenotypic variability within families afflicted by the same disease-linked gene. Individuals that are homozygous for a mutation or heterozygous for two or more mutations often show more severe phenotypes. Secondly, genetic modifiers are present in some cardiomyopathy patients and are associated with a poorer prognosis. At the protein level, changes in protein-protein interactions may also be important in determining the type of cardiomyopathy caused by different mutations. This review provides insight into the complex cardiovascular phenotypes and genetic variability associated with HCM, DCM, RCM and VNCM.

Original languageEnglish (US)
Pages (from-to)899-909
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume48
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

Cardiomyopathies
Phenotype
Restrictive Cardiomyopathy
Mutation
Hypertrophic Cardiomyopathy
Dilated Cardiomyopathy
Sudden Death
Genes
Proteins
Heart Transplantation
Cardiac Arrhythmias
Young Adult
Cause of Death
Heart Failure
Population

Keywords

  • Cardiomyopathy
  • Dilated
  • Familial
  • Hypertrophic
  • Restrictive
  • Sarcomere
  • Ventricular noncompaction

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Malignant and benign mutations in familial cardiomyopathies : Insights into mutations linked to complex cardiovascular phenotypes. / Xu, Qian; Dewey, Shannamar; Nguyen, Susan; Gomes, Aldrin V.

In: Journal of Molecular and Cellular Cardiology, Vol. 48, No. 5, 05.2010, p. 899-909.

Research output: Contribution to journalArticle

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