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

Lopes, Luis RGarcia-Hernández, SoledadLorenzini, MassimilianoFutema, MartaChumakova, OlgaZateyshchikov, DmitryIsidoro-Garcia, MariaVillacorta, EduardoEscobar-Lopez, LuisGarcia-Pavia, PabloBilbao, RaquelDobarro, DavidSandin-Fuentes, MariaCatalli, ClaudioGener Querol, BlancaMezcua, AinhoaGarcia Pinilla, JoseBloch Rasmussen, TorstenFerreira-Aguar, AnaRevilla-Martí, PabloBasurte Elorz, Maria TeresaBautista Paves, AliciaRamon Gimeno, JuanFigueroa, Ana VirginiaFranco-Gutierrez, RaulFuentes-Cañamero, Maria EugeniaMartinez Moreno, MarinaOrtiz-Genga, MartinPiqueras-Flores, JesusAnalia Ramos, KarinaRudzitis, AinarsRuiz-Guerrero, LuisStein, RicardoTriguero-Bocharán, Maytede la Higuera, LuisOchoa, Juan PabloAbu-Bonsrah, DadKwok, Cecilia Y TSmith, Jacob BPorrello, Enzo RAkhtar, Mohammed MJager, JoannaAshworth, MichaelSyrris, PetrosElliott, David AMonserrat, LorenzoElliott, Perry M2023-02-092023-02-092021http://hdl.handle.net/10668/18201The 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/ALPK3GeneticsHypertrophic cardiomyopathyCardiomyopathy, HypertrophicHeterozygoteHumansMuscle ProteinsMutationProtein KinasesSarcomeresAlpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy.research article34263907open access10.1093/eurheartj/ehab4241522-9645PMC8380059https://academic.oup.com/eurheartj/article-pdf/42/32/3063/46627240/ehab424.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380059/pdf