ALPK3-deficient cardiomyocytes generated from patient-derived induced pluripotent stem cells and mutant human embryonic stem cells display abnormal calcium handling and establish that ALPK3 deficiency underlies familial cardiomyopathy

DG Phelan; DJ Anderson; SE Howden; RCB Wong; PF Hickey; K Pope; GR Wilson; A Pébay; AM Davis; S Petrou; AG Elefanty; EG Stanley; PA James; I Macciocca; M Bahlo; MM Cheung; DJ Amor; DA Elliott; PJ Lockhart

Journal article

ALPK3-deficient cardiomyocytes generated from patient-derived induced pluripotent stem cells and mutant human embryonic stem cells display abnormal calcium handling and establish that ALPK3 deficiency underlies familial cardiomyopathy

DG Phelan, DJ Anderson, SE Howden, RCB Wong, PF Hickey, K Pope, GR Wilson, A Pébay, AM Davis, S Petrou, AG Elefanty, EG Stanley, PA James, I Macciocca, M Bahlo, MM Cheung, DJ Amor, DA Elliott, PJ Lockhart

European Heart Journal | OXFORD UNIV PRESS | Published : 2016

DOI: 10.1093/eurheartj/ehw160

Abstract

Aims We identified a novel homozygous truncating mutation in the gene encoding alpha kinase 3 (ALPK3) in a family presenting with paediatric cardiomyopathy. A recent study identified biallelic truncating mutations of ALPK3 in three unrelated families; therefore, there is strong genetic evidence that ALPK3 mutation causes cardiomyopathy. This study aimed to clarify the mutation mechanism and investigate the molecular and cellular pathogenesis underlying ALPK3-mediated cardiomyopathy. Methods and results We performed detailed clinical and genetic analyses of a consanguineous family, identifying a new ALPK3 mutation (c.3792G>A, p.W1264X) which undergoes nonsense-mediated decay in ex vivo and in..

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University of Melbourne Researchers

Peter Hickey Author

Alice Pebay Author

Andrew Davis Author

Andrew Elefanty Author

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Grants

Awarded by European Commission

Funding Acknowledgements

This work was supported by the Victorian Government's Operational Infrastructure Support Program and Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme (NHMRC IRIISS). Funding was provided by the National Health and Medical Research Council/Heart Foundation grant-in-aid (G 12M 6401). D.J.A. is supported by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement PIOF-GA-2010-276186. A.P. is supported by an Australian Research Council Future Fellowship (FT140100047). A.G.E. and E.G.S. are supported by National Health and Medical Research Council Senior Research Fellowships (GNT1002154 and GNT1079004). M.B. is supported by an National Health and Medical Research Council Senior Research Fellowship (GNT1002098) and an National Health and Medical Research Council Program grant (GNT1054618). P.J.L. is supported by an National Health and Medical Research Council Career Development Fellowship (GNT1032364).