Variants in NKX2-5 and FLNC Cause Dilated Cardiomyopathy and Sudden Cardiac Death.

• Published in: Circulation: Genomic and Precision Medicine
• Main Authors: Sveinbjornsson, Gardar, Olafsdottir, Eva F, Thorolfsdottir, Rosa B, Davidsson, Olafur B, Helgadottir, Anna, Jonasdottir, Adalbjorg, Jonasdottir, Aslaug, Bjornsson, Eythor, Jensson, Brynjar O, Arnadottir, Gudny A, Kristinsdottir, Hallfridur, Stephensen, Sigurdur S, Oskarsson, Gylfi, Gudbjartsson, Tomas, Sigurdsson, Emil L, Andersen, Karl, Danielsen, Ragnar, Arnar, David O, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, Sulem, Patrick, Thorgeirsson, Gudmundur, Gudbjartsson, Daniel F, Holm, Hilma, Stefansson, Kari
• Other Authors: 1 deCODE genetics/Amgen, Inc, Reykjavik, Iceland (G.S., E.F.O., R.B.T., O.B.D., A.H. 2 School of Engineering and Natural Sciences (G.S., D.F.G.). 3 Faculty of Medicine (E.F.O., E.B., H.K., T.G., K.A., D.O.A., I.J., U.T., G.T., K.S.). 4 Adalbjorg Jonasdottir, Aslaug Jonasdottir, E.B., B.O.J., G.A.A., D.O.A., I.J., U.T., P.S., G.T., D.F.G., H.H., K.S.). 5 Department of Pediatric Cardiology, Children's Hospital Reykjavik, Iceland (S.S.S., G.O.). 6 Department of Cardiothoracic Surgery (T.G.). 7 Department of Family Medicine (E.L.S.), University of Iceland, Reykjavik. 8 Department of Development, Primary Health Care of the Capital Area, Reykjavik, Iceland (E.L.S.). 9 Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland (K.A., R.D., D.O.A., G.T.). 10 Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik (I.J.).
• Format: Article in Journal/Newspaper
• Language: English
• Published: Lippincott Williams & Wilkins 2018
• Subjects: atrioventricular block; cardiomyopathies; genome-wide association study; heart failure; penetrance; whole genome sequencing; Hjartabilun; Hjartasjúkdómar; Gen; Arfgengi; Cardiomyopathy; Dilated; Iceland
• Online Access: http://hdl.handle.net/2336/620718; https://doi.org/10.1161/CIRCGEN.117.002151

To access publisher's full text version of this article click on the hyperlink below Dilated cardiomyopathy (DCM) is an important cause of heart failure. Variants in >50 genes have been reported to cause DCM, but causative variants have been found in less than half of familial cases. Variants causing DCM in Iceland have not been reported before. We performed a genome-wide association study on DCM based on whole genome sequencing. We tested the association of 32.5 million sequence variants in 424 cases and 337 689 population controls in Iceland. We identified 2 DCM variants in established cardiomyopathy genes, a missense variant p.Phe145Leu in NKX2-5 carried by 1 in 7100 Icelanders ( P=7.0×10 Two rare variants in NKX2-5 and FLNC, carried by 1 in 2400 Icelanders, cause familial DCM in Iceland. These genes have recently been associated with DCM. Given the serious consequences of these variants, we suggest screening for them in individuals with DCM and their family members, with subsequent monitoring of carriers, offering early intervention.