Details

Autor(en) / Beteiligte

• Kramer, Ryan J
• Fatahian, Amir Nima
• Chan, Alice
• Mortenson, Jeffery
• Osher, Jennifer
• Sun, Bo
• Parker, Lauren E
• Rosamilia, Michael B
• Potter, Kyra B
• Moore, Kaila
• Atkins, Sage L
• Rosenfeld, Jill A
• Birjiniuk, Alona
• Jones, Edward
• Howard, Taylor S
• Kim, Jeffrey J
• Scott, Daryl A
• Lalani, Seema
• Rouzbehani, Omid M T
• Kaplan, Samantha
• Hathaway, Marissa A
• Cohen, Jennifer L
• Asaki, S Yukiko
• Martinez, Hugo R
• Boudina, Sihem
• Landstrom, Andrew P

Titel

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

Ist Teil von

• Circulation. Genomic and precision medicine, 2023-08, Vol.16 (4), p.390-400

Ort / Verlag

United States

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor . Early studies suggest that deletion of may underlie cardiomyopathy in patients with 1p36 deletion; however, the prognostic impact of loss is unknown. 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 knockout mouse ( 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. The retrospective cohort included 71 patients. Among individuals with deleted, 34.5% developed cardiomyopathy versus 7.7% of individuals with not deleted ( =0.1). In the combined retrospective and systematic review cohort (n=134), deletion-associated cardiomyopathy risk was recapitulated and significant (29.1% versus 10.8%, =0.03). deletion was associated with increased risk of death, cardiac transplant, or ventricular assist device ( =0.04). Among those deleted, 34.5% of females developed cardiomyopathy versus 16.7% of their male counterparts ( =0.2). We find sex-specific differences in the incidence and the severity of contractile dysfunction and fibrosis in female conditional knockout mice. Further, female conditional knockout mice demonstrate significantly elevated risk of mortality ( =0.0003). deletion is associated with a significantly increased risk of cardiomyopathy and cardiac mortality. conditional knockout mice develop cardiomyopathy in a sex-biased way. Patients with deletion should be assessed for cardiac disease.