Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy

Eur Heart J. 2014 Aug 21;35(32):2165-73. doi: 10.1093/eurheartj/ehu050. Epub 2014 Feb 20.


Aim: Peripartum cardiomyopathy (PPCM) can be an initial manifestation of familial dilated cardiomyopathy (DCM). We aimed to identify mutations in families that could underlie their PPCM and DCM.

Methods and results: We collected 18 families with PPCM and DCM cases from various countries. We studied the clinical characteristics of the PPCM patients and affected relatives, and applied a targeted next-generation sequencing (NGS) approach to detect mutations in 48 genes known to be involved in inherited cardiomyopathies. We identified 4 pathogenic mutations in 4 of 18 families (22%): 3 in TTN and 1 in BAG3. In addition, we identified 6 variants of unknown clinical significance that may be pathogenic in 6 other families (33%): 4 in TTN, 1 in TNNC1, and 1 in MYH7. Measurements of passive force in single cardiomyocytes and titin isoform composition potentially support an upgrade of one of the variants of unknown clinical significance in TTN to a pathogenic mutation. Only 2 of 20 PPCM cases in these families showed the recovery of left ventricular function.

Conclusion: Targeted NGS shows that potentially causal mutations in cardiomyopathy-related genes are common in families with both PPCM and DCM. This supports the earlier finding that PPCM can be part of familial DCM. Our cohort is particularly characterized by a high proportion of TTN mutations and a low recovery rate in PPCM cases.

Keywords: Cardiomyopathy; Genetics; Peripartum cardiomyopathy; Pregnancy; Titin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiomyopathies / genetics*
  • Cardiomyopathy, Dilated / genetics
  • Cohort Studies
  • Connectin / genetics*
  • Female
  • Humans
  • Mutation / genetics*
  • Pedigree
  • Puerperal Disorders / genetics*
  • STAT3 Transcription Factor / genetics
  • Young Adult


  • Connectin
  • STAT3 Transcription Factor
  • STAT3 protein, human

Supplementary concepts

  • Familial dilated cardiomyopathy