Assays of Variant Effect and Automated Patch Clamping Improve KCNH2 -LQTS Variant Classification and Cardiac Event Risk Stratification.

Autor: O'Neill MJ; Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, TN (M.J.O., X.B.)., Ng CA; Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia (C.-A.N., Q.S., C.-Y.T., J.I.V.).; School of Clinical Medicine, UNSW Sydney, Darlinghurst, NSW, Australia (C.-A.N., J.I.V.)., Aizawa T; Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan (T.A., A.K.)., Sala L; IRCCS, Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy (L.S.).; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy (L.S., L.C., F.D., G.M., C.S., P.J.S.)., Bains S; Department of Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN (S.B., R.N., J.M.B., J.R.G., M.J.A.)., Winbo A; Department of Physiology, University of Auckland, New Zealand. (A.W., B.M.K.)., Ullah R; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Shen Q; Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia (C.-A.N., Q.S., C.-Y.T., J.I.V.)., Tan CY; Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia (C.-A.N., Q.S., C.-Y.T., J.I.V.)., Kozek K; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Vanags LR; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Mitchell DW; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Shen A; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Wada Y; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Kashiwa A; Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan (T.A., A.K.)., Crotti L; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy (L.S., L.C., F.D., G.M., C.S., P.J.S.).; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Dagradi F; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy (L.S., L.C., F.D., G.M., C.S., P.J.S.)., Musu G; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy (L.S., L.C., F.D., G.M., C.S., P.J.S.)., Spazzolini C; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy (L.S., L.C., F.D., G.M., C.S., P.J.S.)., Neves R; Department of Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN (S.B., R.N., J.M.B., J.R.G., M.J.A.)., Bos JM; Department of Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN (S.B., R.N., J.M.B., J.R.G., M.J.A.)., Giudicessi JR; Department of Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN (S.B., R.N., J.M.B., J.R.G., M.J.A.)., Bledsoe X; Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, TN (M.J.O., X.B.)., Gamazon ER; Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (E.R.G.)., Lancaster MC; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Glazer AM; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Knollmann BC; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Roden DM; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. (R.U., K.K., L.R.V., D.W.M., A.S., Y.W., L.C., M.C.L., A.M.G., B.C.K., D.M.R.)., Weile J; Department of Medicine and Surgery, University Milano Bicocca, Milan, Italy. Department of Molecular Genetics, University of Toronto, Canada (J.W., F.R.)., Roth F; Department of Medicine and Surgery, University Milano Bicocca, Milan, Italy. Department of Molecular Genetics, University of Toronto, Canada (J.W., F.R.)., Salem JE; Sorbonne University, APHP, INSERM, Clinical Pharmacology, Hopital Pitié-Salpétière Department of Medicine, University of Auckland, New Zealand. (J.-E.S.)., Earle N; Department of Cardiology, Waikato Hospital, Hamilton, New Zealand (N.E., R.S.)., Stiles R; Department of Cardiology, Waikato Hospital, Hamilton, New Zealand (N.E., R.S.)., Agee T; Department of Chemistry, Mississippi State University, Starkville (T.A., C.N.J.)., Johnson CN; Department of Chemistry, Mississippi State University, Starkville (T.A., C.N.J.)., Horie M; Department of Cardiovascular Medicine, Shiga University of Medical Science, Japan (M.H.)., Skinner J; Sydney Children's Hospital Network, University of Sydney, Australia (J.S.)., Ackerman MJ; Department of Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN (S.B., R.N., J.M.B., J.R.G., M.J.A.)., Schwartz PJ; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy (L.S., L.C., F.D., G.M., C.S., P.J.S.)., Ohno S; Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Osaka, Japan (S.O.)., Vandenberg JI; Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia (C.-A.N., Q.S., C.-Y.T., J.I.V.).; School of Clinical Medicine, UNSW Sydney, Darlinghurst, NSW, Australia (C.-A.N., J.I.V.)., Kroncke BM; Department of Physiology, University of Auckland, New Zealand. (A.W., B.M.K.).

Publikováno v: Circulation [Circulation] 2024 Sep 24. Date of Electronic Publication: 2024 Sep 24.

Multicenter clinical and functional evidence reclassifies a recurrent noncanonical filamin C splice-altering variant.

Autor: O'Neill MJ; Vanderbilt University School of Medicine, Medical Scientist Training Program, Vanderbilt University, Nashville, Tennessee., Chen SN; Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado., Rumping L; Department of Human Genetics, Amsterdam UMC, Amsterdam, The Netherlands., Johnson R; Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia., van Slegtenhorst M; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands., Glazer AM; Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee., Yang T; Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee., Solus JF; Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee., Laudeman J; Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee., Mitchell DW; Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee., Vanags LR; Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee., Kroncke BM; Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee., Anderson K; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Gao S; Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado., Verdonschot JAJ; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands., Brunner H; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands., Hellebrekers D; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands., Taylor MRG; Department of Human Genetics, Amsterdam UMC, Amsterdam, The Netherlands., Roden DM; Departments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee., Wessels MW; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands., Lekanne Dit Deprez RH; Department of Human Genetics, Amsterdam UMC, Amsterdam, The Netherlands., Fatkin D; Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia; Cardiology Department, St. Vincent's Hospital, Sydney, NSW, Australia., Mestroni L; Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado., Shoemaker MB; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: moore.b.shoemaker@vumc.org.

Publikováno v: Heart rhythm [Heart Rhythm] 2023 Aug; Vol. 20 (8), pp. 1158-1166. Date of Electronic Publication: 2023 May 09.

High-throughput discovery of trafficking-deficient variants in the cardiac potassium channel K V 11.1.

Autor: Kozek KA; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Glazer AM; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Ng CA; Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia; St Vincent's Clinical School, UNSW Sydney, Darlinghurst, New South Wales, Australia., Blackwell D; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Egly CL; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Vanags LR; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Blair M; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Mitchell D; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Matreyek KA; Department of Genome Sciences, University of Washington, Seattle, Washington., Fowler DM; Department of Genome Sciences, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington., Knollmann BC; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Vandenberg JI; Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia; St Vincent's Clinical School, UNSW Sydney, Darlinghurst, New South Wales, Australia., Roden DM; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Kroncke BM; Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: brett.m.kroncke.1@vumc.org.

Publikováno v: Heart rhythm [Heart Rhythm] 2020 Dec; Vol. 17 (12), pp. 2180-2189. Date of Electronic Publication: 2020 Jun 06.