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KBTBD13 is a novel cardiomyopathy gene.

Josine M de WinterKarlijn BoumanJoshua StromMei MethawasinJan D H JongbloedWilma van der RoestJan van WijngaardenJanneke TimmermansRobin NijveldtFrederik van den HeuvelErik-Jan KamsteegBaziel G van EngelenRicardo GalliSylvia J P BogaardsReinier A BoonRobbert J van der PijlHenk GranzierBobby KoelemanAhmad S AminJolanda van der VeldenJ Peter van TintelenMaarten P van den BergKarin Y van Spaendonck-ZwartsNicol C VoermansCoen A C Ottenheijm
Published in: Human mutation (2022)
KBTBD13 variants cause nemaline myopathy type 6 (NEM6). The majority of NEM6 patients harbors the Dutch founder variant, c.1222C>T, p.Arg408Cys (KBTBD13 p.R408C). Although KBTBD13 is expressed in cardiac muscle, cardiac involvement in NEM6 is unknown. Here, we constructed pedigrees of three families with the KBTBD13 p.R408C variant. In 65 evaluated patients, 12% presented with left ventricle dilatation, 29% with left ventricular ejection fraction< 50%, 8% with atrial fibrillation, 9% with ventricular tachycardia, and 20% with repolarization abnormalities. Five patients received an implantable cardioverter defibrillator, three cases of sudden cardiac death were reported. Linkage analysis confirmed cosegregation of the KBTBD13 p.R408C variant with the cardiac phenotype. Mouse studies revealed that (1) mice harboring the Kbtbd13 p.R408C variant display mild diastolic dysfunction; (2) Kbtbd13-deficient mice have systolic dysfunction. Hence, (1) KBTBD13 is associated with cardiac dysfunction and cardiomyopathy; (2) KBTBD13 should be added to the cardiomyopathy gene panel; (3) NEM6 patients should be referred to the cardiologist.
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