Journal article

Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy

Luis R Lopes, Soledad Garcia-Hernandez, Massimiliano Lorenzini, Marta Futema, Olga Chumakova, Dmitry Zateyshchikov, Maria Isidoro-Garcia, Eduardo Villacorta, Luis Escobar-Lopez, Pablo Garcia-Pavia, Raquel Bilbao, David Dobarro, Maria Sandin-Fuentes, Claudio Catalli, Blanca Gener Querol, Ainhoa Mezcua, Jose Garcia Pinilla, Torsten Bloch Rasmussen, Ana Ferreira-Aguar, Pablo Revilla-Marti Show all



AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm..

View full abstract


Awarded by Medical Research Council (MRC) Clinical Academic Research Partnership (CARP) award

Awarded by British Heart Foundation Program Grant

Funding Acknowledgements

Luis R Lopes is funded by a Medical Research Council (MRC) Clinical Academic Research Partnership (CARP) award (MR/T005181/1). The work at UCL was funded by the British Heart Foundation Program Grant (RG/15/8/31480) and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Other funding includes grant and fellowship support from National Health and Medical Research Council of Australia (E.R.P., D.A.E.), Australian Research Council (E.R.P.), Heart Foundation of Australia (E.R.P.), The Stafford Fox Medical Research Foundation (E.R.P., D.A.E.), and the Royal Children's Hospital Foundation (D.A.-B., E.R.P., D.A.E.).