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

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

Abstract 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...

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Veröffentlicht in:European heart journal 2021-08, Vol.42 (32), p.3063-3073
Hauptverfasser: 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
Format: Artikel
Sprache:eng
Schlagworte:
Cardiomyopathy, Hypertrophic - genetics
Clinical Research
Heterozygote
Humans
Muscle Proteins - genetics
Mutation
Protein Kinases - genetics
Sarcomeres
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Zusammenfassung:Abstract 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 
ISSN:0195-668X
1522-9645
DOI:10.1093/eurheartj/ehab424