Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy.
- Lopes, Luis R
- Garcia-Hernández, Soledad
- Lorenzini, Massimiliano
- Futema, Marta
- Chumakova, Olga
- Zateyshchikov, Dmitry
- Isidoro-Garcia, Maria
- Villacorta, Eduardo
- Escobar-Lopez, Luis
- Garcia-Pavia, Pablo
- Bilbao, Raquel
- Dobarro, David
- Sandin-Fuentes, Maria
- Catalli, Claudio
- Gener Querol, Blanca
- Mezcua, Ainhoa
- Garcia Pinilla, Jose
- Bloch Rasmussen, Torsten
- Ferreira-Aguar, Ana
- Revilla-Martí, Pablo
- Basurte Elorz, Maria Teresa
- Bautista Paves, Alicia
- Ramon Gimeno, Juan
- Figueroa, Ana Virginia
- Franco-Gutierrez, Raul
- Fuentes-Cañamero, Maria Eugenia
- Martinez Moreno, Marina
- Ortiz-Genga, Martin
- Piqueras-Flores, Jesus
- Analia Ramos, Karina
- Rudzitis, Ainars
- Ruiz-Guerrero, Luis
- Stein, Ricardo
- Triguero-Bocharán, Mayte
- de la Higuera, Luis
- Ochoa, Juan Pablo
- Abu-Bonsrah, Dad
- Kwok, Cecilia Y T
- Smith, Jacob B
- Porrello, Enzo R
- Akhtar, Mohammed M
- Jager, Joanna
- Ashworth, Michael
- Syrris, Petros
- Elliott, David A
- Monserrat, Lorenzo
- Elliott, Perry M
DOIAbstract
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. 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 Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype
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