Disease modeling of a mutation in α-actinin 2 guides clinical therapy in hypertrophic cardiomyopathy.
disease modeling
human-induced pluripotent stem cells
hypertrophic cardiomyopathy
long QT syndrome
precision medicine
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
03
07
2019
revised:
08
10
2019
accepted:
09
10
2019
pubmed:
5
11
2019
medline:
28
4
2020
entrez:
5
11
2019
Statut:
ppublish
Résumé
Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease accompanied by structural and contractile alterations. We identified a rare c.740C>T (p.T247M) mutation in ACTN2, encoding α-actinin 2 in a HCM patient, who presented with left ventricular hypertrophy, outflow tract obstruction, and atrial fibrillation. We generated patient-derived human-induced pluripotent stem cells (hiPSCs) and show that hiPSC-derived cardiomyocytes and engineered heart tissues recapitulated several hallmarks of HCM, such as hypertrophy, myofibrillar disarray, hypercontractility, impaired relaxation, and higher myofilament Ca
Identifiants
pubmed: 31680489
doi: 10.15252/emmm.201911115
pmc: PMC6895603
doi:
Substances chimiques
ACTN2 protein, human
0
Actinin
11003-00-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e11115Subventions
Organisme : Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)
Pays : International
Organisme : Bundesministerium für Bildung und Forschung (BMBF)
Pays : International
Organisme : Deutsche Herzstiftung (German Heart Foundation)
ID : F/15/17
Pays : International
Organisme : EC|H2020|H2020 Priority Excellent Science|H2020 European Research Council (ERC)
Pays : International
Organisme : Finnish Cultural Foundation|Pirkanmaan Rahasto (Pirkanmaa Regional Fund)
ID : IndividuHeart, 340248
Pays : International
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 3423/5-1
Pays : International
Organisme : EC|Horizon 2020 Framework Programme (H2020)
ID : AFib-TrainNet - 675351
Pays : International
Organisme : Academy of Finland Centre of Excellence in Body-on-Chip Research
Pays : International
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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