A novel familial truncating mutation in the filamin C gene associated with cardiac arrhythmias

• Published in: European journal of medical genetics 2019-04, Vol.62 (4), p.282-285
• Main Authors: Mangum, Kevin D., Ferns, Sunita J.
• Format: Article
• Language: English
• Subjects: Arrhythmia; Deletion; Filamin C; FLNC; Frameshift mutation
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2018.08.006

The authors report for the first time a novel mutation in the FLNC gene associated with cardiac arrhythmias in two half-siblings. The FLNC gene on chromosome 7q32 encodes filamin C, which stabilizes the actin network within the cardiomyocyte. The proband is an 8-year-old asymptomatic patient with frequent premature ventricular contractions noted on serial monitoring. Interestingly, the proband and his half-brother harbored a heterozygous 13 base pair deletion that resulted in a frameshift mutation and introduction of a premature stop codon. Notably, the proband also had a very tragic family history of sudden death in young individuals involving three generations and five family members. Because of their concerning family history and arrhythmias, both siblings underwent off-label implantable cardiac device placement for primary prevention of sudden cardiac death. Whether or not the FLNC mutation is associated with sudden cardiac death requires additional investigation and is beyond the scope of this manuscript. While previous studies have identified several mutations in the FLNC gene associated with dilated and hypertrophic cardiomyopathies, the goal of this study was to report a novel mutation in the FLNC gene that is associated with cardiac arrhythmias. The current study indicates that this mutation may help identify patients at risk for cardiac arrhythmias who would benefit from further cardiac evaluation.