BibTex format
@article{Schafer:2017:10.1038/ng.3719,
author = {Schafer, S and de, Marvao A and Adami, E and Fiedler, LR and Ng, B and Khin, E and Rackham, O and van, Heesch S and Pua, CJ and Kui, M and Walsh, R and Tayal, U and Prasad, SK and Dawes, TJW and Ko, NSJ and Sim, D and Chan, LLH and Chin, CWL and Mazzarotto, F and Barton, PJ and Kreuchwig, F and de, Kleijn DPV and Totman, T and Biffi, C and Tee, N and Rueckert, D and Schneider, V and Faber, A and Regitz-Zagrosek, V and Seidman, JG and Seidman, CE and Linke, WA and Kovalik, J and O'Regan, D and Ware, JS and Hubner, N and Cook, SA},
doi = {10.1038/ng.3719},
journal = {Nature Genetics},
pages = {46--53},
title = {Titin-truncating variants affect heart function in disease cohorts and the general population},
url = {http://dx.doi.org/10.1038/ng.3719},
volume = {49},
year = {2017}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ~1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease.
AU - Schafer,S
AU - de,Marvao A
AU - Adami,E
AU - Fiedler,LR
AU - Ng,B
AU - Khin,E
AU - Rackham,O
AU - van,Heesch S
AU - Pua,CJ
AU - Kui,M
AU - Walsh,R
AU - Tayal,U
AU - Prasad,SK
AU - Dawes,TJW
AU - Ko,NSJ
AU - Sim,D
AU - Chan,LLH
AU - Chin,CWL
AU - Mazzarotto,F
AU - Barton,PJ
AU - Kreuchwig,F
AU - de,Kleijn DPV
AU - Totman,T
AU - Biffi,C
AU - Tee,N
AU - Rueckert,D
AU - Schneider,V
AU - Faber,A
AU - Regitz-Zagrosek,V
AU - Seidman,JG
AU - Seidman,CE
AU - Linke,WA
AU - Kovalik,J
AU - O'Regan,D
AU - Ware,JS
AU - Hubner,N
AU - Cook,SA
DO - 10.1038/ng.3719
EP - 53
PY - 2017///
SN - 1546-1718
SP - 46
TI - Titin-truncating variants affect heart function in disease cohorts and the general population
T2 - Nature Genetics
UR - http://dx.doi.org/10.1038/ng.3719
UR - http://rdcu.be/mP1y
UR - http://hdl.handle.net/10044/1/42638
VL - 49
ER -