Skip to main content

PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study.

Publication ,  Journal Article
Kramer, RJ; Fatahian, AN; Chan, A; Mortenson, J; Osher, J; Sun, B; Parker, LE; Rosamilia, MB; Potter, KB; Moore, K; Atkins, SL; Rosenfeld, JA ...
Published in: Circ Genom Precis Med
August 2023

BACKGROUND: 1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor PRDM16. Early studies suggest that deletion of PRDM16 may underlie cardiomyopathy in patients with 1p36 deletion; however, the prognostic impact of PRDM16 loss is unknown. METHODS: This retrospective cohort included subjects with 1p36 deletion syndrome from 4 hospitals. Prevalence of cardiomyopathy and freedom from death, cardiac transplantation, or ventricular assist device were analyzed. A systematic review cohort was derived for further analysis. A cardiac-specific Prdm16 knockout mouse (Prdm16 conditional knockout) was generated. Echocardiography was performed at 4 and 6 to 7 months. Histology staining and qPCR were performed at 7 months to assess fibrosis. RESULTS: The retrospective cohort included 71 patients. Among individuals with PRDM16 deleted, 34.5% developed cardiomyopathy versus 7.7% of individuals with PRDM16 not deleted (P=0.1). In the combined retrospective and systematic review cohort (n=134), PRDM16 deletion-associated cardiomyopathy risk was recapitulated and significant (29.1% versus 10.8%, P=0.03). PRDM16 deletion was associated with increased risk of death, cardiac transplant, or ventricular assist device (P=0.04). Among those PRDM16 deleted, 34.5% of females developed cardiomyopathy versus 16.7% of their male counterparts (P=0.2). We find sex-specific differences in the incidence and the severity of contractile dysfunction and fibrosis in female Prdm16 conditional knockout mice. Further, female Prdm16 conditional knockout mice demonstrate significantly elevated risk of mortality (P=0.0003). CONCLUSIONS: PRDM16 deletion is associated with a significantly increased risk of cardiomyopathy and cardiac mortality. Prdm16 conditional knockout mice develop cardiomyopathy in a sex-biased way. Patients with PRDM16 deletion should be assessed for cardiac disease.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Circ Genom Precis Med

DOI

EISSN

2574-8300

Publication Date

August 2023

Volume

16

Issue

4

Start / End Page

390 / 400

Location

United States

Related Subject Headings

  • Transcription Factors
  • Retrospective Studies
  • Multicenter Studies as Topic
  • Mice, Knockout
  • Mice
  • Male
  • Humans
  • Fibrosis
  • Female
  • DNA-Binding Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kramer, R. J., Fatahian, A. N., Chan, A., Mortenson, J., Osher, J., Sun, B., … Landstrom, A. P. (2023). PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study. Circ Genom Precis Med, 16(4), 390–400. https://doi.org/10.1161/CIRCGEN.122.003912
Kramer, Ryan J., Amir Nima Fatahian, Alice Chan, Jeffery Mortenson, Jennifer Osher, Bo Sun, Lauren E. Parker, et al. “PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study.Circ Genom Precis Med 16, no. 4 (August 2023): 390–400. https://doi.org/10.1161/CIRCGEN.122.003912.
Kramer RJ, Fatahian AN, Chan A, Mortenson J, Osher J, Sun B, et al. PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study. Circ Genom Precis Med. 2023 Aug;16(4):390–400.
Kramer, Ryan J., et al. “PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study.Circ Genom Precis Med, vol. 16, no. 4, Aug. 2023, pp. 390–400. Pubmed, doi:10.1161/CIRCGEN.122.003912.
Kramer RJ, Fatahian AN, Chan A, Mortenson J, Osher J, Sun B, Parker LE, Rosamilia MB, Potter KB, Moore K, Atkins SL, Rosenfeld JA, Birjiniuk A, Jones E, Howard TS, Kim JJ, Scott DA, Lalani S, Rouzbehani OMT, Kaplan S, Hathaway MA, Cohen JL, Asaki SY, Martinez HR, Boudina S, Landstrom AP. PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study. Circ Genom Precis Med. 2023 Aug;16(4):390–400.

Published In

Circ Genom Precis Med

DOI

EISSN

2574-8300

Publication Date

August 2023

Volume

16

Issue

4

Start / End Page

390 / 400

Location

United States

Related Subject Headings

  • Transcription Factors
  • Retrospective Studies
  • Multicenter Studies as Topic
  • Mice, Knockout
  • Mice
  • Male
  • Humans
  • Fibrosis
  • Female
  • DNA-Binding Proteins