Familial dilated cardiomyopathy: Effective management of the family to improve prognosis

AbstractDilated cardiomyopathy (DCM) is a major cause of congestive heart failure, sudden cardiac death and cardiac transplantation. Aggregating evidence highlights the genetic origin of DCM. However, DCM is a genetically heterogeneous disorder, and the genetic components underlying DCM in most cases remain unknown.The coding regions and splicing junction sites of theA novel heterozygous TBX20 mutation, p.F256I, was identified in a family with DCM transmitted in an autosomal dominant fashion, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 600 control chromosomes and the altered amino acid was completely conserved evolutionarily among various species. Functional assays revealed that the mutant TBX20 had significantly diminished transcriptional activity. Furthermore, the mutation markedly reduced the synergistic activation of TBX20 with NKX2-5 or GATA4.This study links TBX20 loss-of-function mutation to idiopathic DCM in humans for the first time, providing novel insight into the molecular mechanism underpinning DCM.

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389 Mutations in troponin and tropomyosin that cause familial dilated cardiomyopathy decrease crossbridge cycling speed and Ca-sensitivity

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(05)80233-4 ◽

2005 ◽

Vol 4 (1) ◽

pp. 86-86

Keyword(s):

Dilated Cardiomyopathy ◽

Familial Dilated Cardiomyopathy ◽

Cycling Speed ◽

Ca Sensitivity

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Association of Polymorphisms of Manganese Superoxide Dismutase and Plasma Platelet-activating Factor Acetylhydrolase Genes With Genetic Susceptibility to Non-familial Dilated Cardiomyopathy

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)85334-x ◽

1998 ◽

Vol 31 (2) ◽

pp. 374A

Author(s):

S Ichihara

Keyword(s):

Superoxide Dismutase ◽

Dilated Cardiomyopathy ◽

Genetic Susceptibility ◽

Manganese Superoxide Dismutase ◽

Platelet Activating Factor ◽

Familial Dilated Cardiomyopathy ◽

Platelet Activating Factor Acetylhydrolase ◽

Manganese Superoxide

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A case of familial dilated cardiomyopathy

Ultraschall in der Medizin - European Journal of Ultrasound ◽

10.1055/s-0033-1354991 ◽

2013 ◽

Vol 34 (S 01) ◽

Author(s):

P Hutsteiner ◽

N Jenewein ◽

J Christ ◽

O Ortmann ◽

U Germer

Keyword(s):

Dilated Cardiomyopathy ◽

Familial Dilated Cardiomyopathy

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Localization of a Gene Responsible for Familial Dilated Cardiomyopathy to Chromosome 1q32

Circulation ◽

10.1161/01.cir.92.12.3387 ◽

1995 ◽

Vol 92 (12) ◽

pp. 3387-3389 ◽

Cited By ~ 91

Author(s):

Jean-Bernard Durand ◽

Linda L. Bachinski ◽

Lisa C. Bieling ◽

Grazyna Z. Czernuszewicz ◽

Antoine B. Abchee ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Familial Dilated Cardiomyopathy

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Reassessment of Gene-Elusive Familial Dilated Cardiomyopathy Leading to the Discovery of a Homozygous AARS2 Variant—The Importance of Regular Reassessment of Genetic Findings

Cardiogenetics ◽

10.3390/cardiogenetics11030013 ◽

2021 ◽

Vol 11 (3) ◽

pp. 122-128

Author(s):

Priya Bhardwaj ◽

Christoffer Rasmus Vissing ◽

Niels Kjær Stampe ◽

Kasper Rossing ◽

Alex Hørby Christensen ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Genetic Screening ◽

Sanger Sequencing ◽

Mitochondrial Protein ◽

Trna Synthetase ◽

Familial Dilated Cardiomyopathy ◽

Pathogenic Variants ◽

Case Summary ◽

Heterozygous Carriers ◽

Important Enzyme

Background: AARS2 encodes the mitochondrial protein alanyl-tRNA synthetase 2 (MT-AlaRS), an important enzyme in oxidative phosphorylation. Variants in AARS2 have previously been associated with infantile cardiomyopathy. Case summary: A 4-year-old girl died of infantile-onset dilated cardiomyopathy (DCM) in 1996. Fifteen years later, her 21-year-old brother was diagnosed with DCM and ultimately underwent heart transplantation. Initial sequencing of 15 genes discovered no pathogenic variants in the brother at the time of his diagnosis. However, 9 years later re-screening in an updated screening panel of 129 genes identified a homozygous AARS2 (c.1774C > T) variant. Sanger sequencing of the deceased girl confirmed her to be homozygous for the AARS2 variant, while both parents and a third sibling were all found to be unaffected heterozygous carriers of the AARS2 variant. Discussion: This report underlines the importance of repeated and extended genetic screening of elusive families with suspected hereditary cardiomyopathies, as our knowledge of disease-causing mutations continuously grows. Although identification of the genetic etiology in the reported family would not have changed the clinical management, the genetic finding allows genetic counselling and holds substantial value in identifying at-risk relatives.

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