Pathological and Comprehensive Genetic Investigation of Autopsy Cases of Idiopathic Bradyarrhythmia.

Autor:	Hata Y; Department of Legal Medicine, Faculty of Medicine, University of Toyama., Ichimata S; Department of Legal Medicine, Faculty of Medicine, University of Toyama., Hirono K; Department of Pediatrics, Faculty of Medicine, University of Toyama., Yamaguchi Y; Department of Legal Medicine, Faculty of Medicine, University of Toyama.; Department of Cardiology, Saiseikai Takaoka Hospital., Oku Y; Department of Legal Medicine, Faculty of Medicine, University of Toyama., Ichida F; Department of Pediatrics, International University of Health & Welfare., Nishida N; Department of Legal Medicine, Faculty of Medicine, University of Toyama.
Jazyk:	angličtina
Zdroj:	Circulation journal : official journal of the Japanese Circulation Society [Circ J] 2022 Dec 23; Vol. 87 (1), pp. 111-119. Date of Electronic Publication: 2022 Sep 07.
DOI:	10.1253/circj.CJ-22-0397
Abstrakt:	Background: Idiopathic bradyarrhythmia is considered to be due to pathological degeneration of the cardiac conduction system (CCS) during aging. There appears to have been no comprehensive genetic investigations in patients with idiopathic bradyarrhythmia. Methods and results: Ten autopsy cases with advanced bradyarrhythmia (6 men and 4 women; age: 70-94 years, 81.5±6.9 years; 5 cases each of sinus node dysfunction [SND] and complete atrioventricular block [CAVB]) were genetically investigated by using whole-exome sequencing. Morphometric analysis of the CCS was performed with sex-, age- and comorbidity-matched control cases. As a result, severe loss of nodal cells and distal atrioventricular conduction system were found in SND and CAVB, respectively. However, the conduction tissue loss was not significant in either the atrioventricular node or the proximal bundle of His in CAVB cases. A total of 13 heterozygous potential variants were found in 3 CAVB and 2 SND cases. Of these 13 variants, 4 were missense in the known progressive cardiac conduction disease-related genes: GATA4 and RYR2. In the remaining 9 variants, 5 were loss-of-function mutation with highly possible pathogenicity. Conclusions: In addition to degenerative changes of selectively vulnerable areas in the heart during advancing age, the vulnerability of the CCS, which may be associated with "rare variants of small effect," may also be a contributing factor to the degeneration of CCS, leading to "idiopathic" bradyarrhythmia.
Databáze:	MEDLINE
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