Clinical outcomes associated with sarcomere mutations in hypertrophic cardiomyopathy: a meta-analysis on 7675 individuals

@article{SedaghatHamedani2017ClinicalOA,
  title={Clinical outcomes associated with sarcomere mutations in hypertrophic cardiomyopathy: a meta-analysis on 7675 individuals},
  author={Farbod Sedaghat-Hamedani and Elham Kayvanpour and Oguz Firat Tugrul and Alan Lai and Ali Amr and Jan Haas and Tanja Proctor and Philipp Ehlermann and Katrin Jensen and Hugo A. Katus and Benjamin Meder},
  journal={Clinical Research in Cardiology},
  year={2017},
  volume={107},
  pages={30-41}
}
BackgroundHypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, which goes along with increased risk for sudden cardiac death (SCD). Despite the knowledge about the different causal genes, the relationship between individual genotypes and phenotypes is incomplete.Methods and resultsWe retrieved PubMed/Medline literatures on genotype–phenotype associations in patients with HCM and mutations in MYBPC3, MYH7, TNNT2, and TNNI3. Altogether, 51 studies with 7675 HCM… 
Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy
TLDR
Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.
Compound Mutation in Cardiac Sarcomere Proteins Is Associated with Increased Risk for Major Arrhythmic Events in Pediatric Onset Hypertrophic Cardiomyopathy
TLDR
No association between affected genes and disease severity or progression was identified in this cohort and no differences in functional classification, LV morphology, hypertrophy, systolic and diastolic function, fibrosis and cardiac medication were revealed.
Clinical and Genetic Aspects of Hypertrophic Cardiomyopathy
TLDR
It is observed that female patients with HCM presented at a later age in a worse condition than male patients, and gender has been proposed to impact the phenotype and outcome of HCM.
Myocardial Deformation Analysis in MYBPC3 and MYH7 Related Sarcomeric Hypertrophic Cardiomyopathy—The Graz Hypertrophic Cardiomyopathy Registry
TLDR
It is suggested, that myocardial deformation analysis may not be helpful in concluding on the underlying HCM genotype, and vice versa.
Genotype-Related Clinical Characteristics and Myocardial Fibrosis and Their Association with Prognosis in Hypertrophic Cardiomyopathy
TLDR
Genotypic analysis may add important information to clinical variables in the assessment of long-term risk for HCM patients and genetic variants in patients with HCM are relatively common and are associated with adverse clinical events and myocardial fibrosis on CMR.
Genetic basis of hypertrophic cardiomyopathy in children
TLDR
A definite genetic diagnosis can be reached in nearly 80% with HCM of childhood onset by applying next-generation sequencing and directing further diagnostics by discussing unsolved cases in a multidisciplinary board.
Retrospective analysis of clinical phenotype and prognosis of hypertrophic cardiomyopathy complicated with hypertension
TLDR
It is found that the clinical phenotypes of HCM patients with HTN differed from those of patients with HCM alone, suggesting that HTN may play a pathogenic role in the pathogenesis of hypertensive hypertrophic cardiomyopathy patients.
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References

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Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese population.
Sarcomere Protein Gene Mutations in Patients With Apical Hypertrophic Cardiomyopathy
TLDR
Only 13% of patients with apical HCM were found to be genotype positive, indicating that genome-wide association studies and gene expression profiling are needed for better understanding of the genetic background of the disease.
Spectrum and clinical manifestations of mutations in genes responsible for hypertrophic cardiomyopathy
TLDR
The most common gene responsible for HCM in the study population was MYBPC3, followed by MYH7, TNNI3 and TNNT2, and differences in both frequency and distribution of mutations of the two most common genes compared to other populations are discovered.
Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy.
TLDR
This study demonstrated the frequency and distribution of mutations in a large cohort of familial HCM in Japan and found several mutations were found in multiple unrelated proband patients, for which the geographic distribution suggested founder effects of the mutations.
[Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy].
Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene
TLDR
MYBPC3 mutations can be associated with cardiac events such as progressive heart failure, stroke and sudden death even at younger age, therefore, patients with MYB PC3 mutations require thorough clinical risk assessment.
Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy.
TLDR
Screening for sarcomere protein gene mutations in HCM identifies a broad subgroup of patients with increased propensity toward long-term impairment of left ventricular function and adverse outcome, irrespective of the myofilament (thick, intermediate, or thin) involved.
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