P1392
Next generation sequencing in lone atrial fibrillation patients

Abstract

Background. Minor part of atrial fibrillation (AF) patients develops the disease without any well-known risk factors, which is a particular form of the disease, known as a lone AF. Rare genetic variants were described as causative for lone AF. The aim of this study was to investigate occurrence of rare genetic variants in lone AF patients.

Material and Methods. We performed Mendeliome sequencing for 21 lone AF patients. Lone AF was defined as AF in individuals younger than 65 years in the absence of cardiovascular or structural heart disease, endocrinologic or pulmonary disease, chronic kidney disease, obesity and excessive alcohol consumption. Data analysis was performed by current laboratory pipeline. We analyzed 453 cardiomyopathy, arrhythmias and sudden cardiac death related genes.

Results. In eight out of 21 (38%) lone AF patients rare likely pathogenic variants were found (Table 1.). Seven rare truncating TTN variants and one LMNA missense variant were observed. Four unrelated patients were positive for the same TTN variant c.13696 C > T; p.(Gln4566Ter). The same variant was previously found in ARVC patient in our laboratory. Segregation analysis and phenotyping of relatives is ongoing.

Conclusions. Rare genetic variants are common causes of the lone atrial fibrillation. TTN gene variant c.13696C > T; p.(Gln4566Ter) is a potential founder variant in the Baltic population.

Table 1. Genetic variants in lone AF

Gender	Age of AF onset	Genetic variant	Family history
Male	53	LMNA: p.(Ser326Thr)	AF in mother
Male	11	TTN: p.(Trp31854Ter)	AF in father
Male	30	TTN: p.(GLn4566Ter)	AF in uncle
Female	45	TTN: p.(GLn4566Ter)	Negative
Male	37	TTN: p.(GLn4566Ter)	AF in father
Male	25	TTN: p.(GLn4566Ter)	AF in father, maternal and paternal grandmother
Female	60	TTN: p.(Arg27414Ter)	Sudden cardiac death at the age of 50 in grand father
Female	52	TTN: p.(Arg1012Ter)	AF in mother