Clinical Research in Cardiology

, Volume 106, Issue 2, pp 127–139 | Cite as

Genotype-phenotype associations in dilated cardiomyopathy: meta-analysis on more than 8000 individuals

  • Elham Kayvanpour
  • Farbod Sedaghat-Hamedani
  • Ali Amr
  • Alan Lai
  • Jan Haas
  • Daniel B. Holzer
  • Karen S. Frese
  • Andreas Keller
  • Katrin Jensen
  • Hugo A. Katus
  • Benjamin MederEmail author
Original Paper



Routine genetic testing in Dilated Cardiomyopathy (DCM) has recently become reality using Next-Generation Sequencing. Several studies have explored the relationship between genotypes and clinical phenotypes to support risk estimation and therapeutic decisions, however, most studies are small or restricted to a few genes. This study provides to our knowledge the first systematic meta-analysis on genotype-phenotype associations in DCM.

Methods and results

We retrieved PubMed/Medline literature on genotype–phenotype associations in patients with DCM and mutations in LMNA, PLN, RBM20, MYBPC3, MYH7, TNNT2 and TNNI3. We summarized and extensively reviewed all studies that passed selection criteria and performed a meta-analysis on key phenotypic parameters. Together, 48 studies with 8097 patients were included. Furthermore, we reviewed recent studies investigating genotype-phenotype associations in DCM patients with TTN mutations. The average frequency of mutations in the investigated genes was between 1 and 5 %. The mean age of DCM onset was the beginning of the fifth decade for all genes. Heart transplantation (HTx) rate was highest in LMNA mutation carriers (27 %), while RBM20 mutation carriers were transplanted at a markedly younger age (mean 28.5 years). While 73 % of DCM patients with LMNA mutations showed cardiac conduction diseases, low voltage was the reported ECG hallmark in PLN mutation carriers. The frequency of ventricular arrhythmia in DCM patients with LMNA (50 %) and PLN (43 %) mutations was significantly higher. The penetrance of DCM phenotype in subjects with TTN truncating variants increased with age and reached 100 % by age of 70.


A pooled analysis of available genotype-phenotype data shows a higher prevalence of sudden cardiac death (SCD), cardiac transplantation, or ventricular arrhythmias in LMNA and PLN mutation carriers compared to sarcomeric gene mutations. This study will further support the clinical interpretation of genetic findings.


DCM Phenotype-genotype associations Meta-analysis 


Compliance with ethical standards

Conflict of interest

None declared.


This work was supported by European Union (FP7 INHERITANCE and BestAgeing), the “Bundesministerium für Bildung und Forschung” (BMBF): German Center for Cardiovascular Research (DZHK) and German Society of Cardiology (DGK). There are no relationships with industry.

Supplementary material

392_2016_1033_MOESM1_ESM.pdf (3.3 mb)
Supplementary material 1 (PDF 3413 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Elham Kayvanpour
    • 1
    • 2
  • Farbod Sedaghat-Hamedani
    • 1
    • 2
  • Ali Amr
    • 1
    • 2
  • Alan Lai
    • 1
  • Jan Haas
    • 1
    • 2
  • Daniel B. Holzer
    • 1
  • Karen S. Frese
    • 1
    • 2
  • Andreas Keller
    • 3
  • Katrin Jensen
    • 4
  • Hugo A. Katus
    • 1
    • 2
  • Benjamin Meder
    • 1
    • 2
    Email author
  1. 1.Department of Medicine IIIUniversity of HeidelbergHeidelbergGermany
  2. 2.DZHK (German Centre for Cardiovascular Research)BerlinGermany
  3. 3.Clinical BioinformaticsSaarland UniversitySaarbrückenGermany
  4. 4.Institute of Medical Biometry and InformaticsUniversity of HeidelbergHeidelbergGermany

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