{"id":6254,"date":"2023-02-17T07:12:50","date_gmt":"2023-02-17T07:12:50","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2018-multifocal-atrial-and-ventricular-premature-contractions-with-an-increased-risk-of-dilated-cardiomyopathy-caused-by-a-nav1-5-gain-of-function-mutation-g213d\/"},"modified":"2023-02-17T07:12:51","modified_gmt":"2023-02-17T07:12:51","slug":"2018-multifocal-atrial-and-ventricular-premature-contractions-with-an-increased-risk-of-dilated-cardiomyopathy-caused-by-a-nav1-5-gain-of-function-mutation-g213d","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2018-multifocal-atrial-and-ventricular-premature-contractions-with-an-increased-risk-of-dilated-cardiomyopathy-caused-by-a-nav1-5-gain-of-function-mutation-g213d\/","title":{"rendered":"2018 &#8211; Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a NaV1.5 gain-of-function mutation (G213D)"},"content":{"rendered":"<p>Background: SCN5A mutations can lead to different cardiac diseases. Recently, SCN5A mutations have been linked to the clinical entity multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by ventricular ectopy and dilated cardiomyopathy. Methods &#038; Results: A family with a uniform MEPPC-like phenotype, associated with complex atrial and ventricular arrhythmias and dilated cardiomyopathy caused by a high frequency of ventricular ectopy was clinically assessed. Screening of the SCN5A gene revealed a missense mutation in the linker between segments 3 and 4 in domain 1 of the NaV1.5 protein, resulting in a glycine to aspartate substitution at position 213 (G213D). The phenotype co-segregated with the missense mutation. Electrophysiological studies of wild type (WT) hNaV1.5 and hNaV1.5_G213D expressed in CHO-K cells showed that the voltage of half-maximal activation (V\u00bd) was significantly more negative for hNaV1.5_G213D compared to WT (V\u00bd\u2005=\u2005\u221238.7\u2005\u00b1\u20050.5\u2005mV for WT and V\u00bd\u2005=\u2005\u221242.4\u2005\u00b1\u20050.5\u2005mV for G213D; P\u2005<\u20050.001). This suggests activation of NaV1.5_G231D at more negative potentials. The V\u00bd of steady-state inactivation was significantly shifted towards more positive values for NaV1.5_G213D (V\u00bd\u2005=\u2005\u221286.7\u2005\u00b1\u20050.2\u2005mV for WT and \u221282.2\u2005\u00b1\u20050.3\u2005mV for G213D; P\u2005<\u20050.001), also contributing to a gain-of-function phenotype. Flecainide and amiodarone markedly reduced premature atrial and ventricular contractions in four patients. Conclusion: The NaV1.5_G213D mutation is associated with a gain-of-function phenotype, multifocal atrial and ventricular ectopy and dilated cardiomyopathy. Since patients with a MEPPC-like phenotype may specifically benefit from Class-1 antiarrhythmic drugs or amiodarone, clinical identification of this disease entity is important. Note: Electrophysiological analysis of heteromers (NaV1.5 and\u00a0NaV1.5_G213D mutation) were executed on the SyncroPatch 384PE. Data are not shown in the publication.\n<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[54],"target_categories":[61],"target_families":[332],"targets":[93],"resource_keyword":[],"class_list":["post-6254","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","therapeutic_areas-cardiac-safety-cipa","target_categories-voltage-gated-ion-channels","target_families-nav-channels","targets-nav1-5"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6254","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6254"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6254"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6254"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6254"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6254"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6254"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6254"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6254"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6254"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}