JACC: Basic to Translational Science (Aug 2016)
FLNC Gene Splice Mutations Cause Dilated Cardiomyopathy
- Rene L. Begay, BS,
- Charles A. Tharp, MD,
- August Martin,
- Sharon L. Graw, PhD,
- Gianfranco Sinagra, MD,
- Daniela Miani, MD,
- Mary E. Sweet, BA,
- Dobromir B. Slavov, PhD,
- Neil Stafford, MD,
- Molly J. Zeller,
- Rasha Alnefaie,
- Teisha J. Rowland, PhD,
- Francesca Brun, MD,
- Kenneth L. Jones, PhD,
- Katherine Gowan,
- Luisa Mestroni, MD,
- Deborah M. Garrity, PhD,
- Matthew R.G. Taylor, MD, PhD
Affiliations
- Rene L. Begay, BS
- Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado
- Charles A. Tharp, MD
- Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado
- August Martin
- Center for Cardiovascular Research, Colorado State University, Fort Collins, Colorado
- Sharon L. Graw, PhD
- Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado
- Gianfranco Sinagra, MD
- Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy
- Daniela Miani, MD
- Department of Cardiothoracic Science, University Hospital S. Maria della Misericordia, Udine, Italy
- Mary E. Sweet, BA
- Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado
- Dobromir B. Slavov, PhD
- Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado
- Neil Stafford, MD
- Center for Cardiovascular Research, Colorado State University, Fort Collins, Colorado
- Molly J. Zeller
- Center for Cardiovascular Research, Colorado State University, Fort Collins, Colorado
- Rasha Alnefaie
- Center for Cardiovascular Research, Colorado State University, Fort Collins, Colorado
- Teisha J. Rowland, PhD
- Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado
- Francesca Brun, MD
- Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy
- Kenneth L. Jones, PhD
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado
- Katherine Gowan
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado
- Luisa Mestroni, MD
- Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado
- Deborah M. Garrity, PhD
- Center for Cardiovascular Research, Colorado State University, Fort Collins, Colorado
- Matthew R.G. Taylor, MD, PhD
- Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado
- DOI
- https://doi.org/10.1016/j.jacbts.2016.05.004
- Journal volume & issue
-
Vol. 1,
no. 5
pp. 344 – 359
Abstract
A genetic etiology has been identified in 30% to 40% of dilated cardiomyopathy (DCM) patients, yet only 50% of these cases are associated with a known causative gene variant. Thus, in order to understand the pathophysiology of DCM, it is necessary to identify and characterize additional genes. In this study, whole exome sequencing in combination with segregation analysis was used to identify mutations in a novel gene, filamin C (FLNC), resulting in a cardiac-restricted DCM pathology. Here we provide functional data via zebrafish studies and protein analysis to support a model implicating FLNC haploinsufficiency as a mechanism of DCM.
Keywords
