Filamin C Truncating Variant Causes Severe Conduction Defects and Mild Cardiomyopathy

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Genetic Basis of Cardiomyopathy

Background:

• Filamin C (FLNC) is crucial for cardiomyocyte structure and signaling.
• FLNC truncating variants are typically associated with severe dilated cardiomyopathy.
• Cardiac conduction defects can be a manifestation of inherited cardiomyopathies.

Observation:

• A 70-year-old female presented with advanced conduction defects requiring pacemaker implantation.
• Cardiac MRI showed mild hypertrophic cardiomyopathy.
• A familial history of cardiac conduction defects suggested a genetic etiology.

Findings:

• Whole-exome sequencing identified a novel FLNC truncating variant (NM_001458.5 FLNC:c.592_593del, p.Cys198Argfs*40).
• This variant was associated with predominantly advanced conduction defects, not severe dilated cardiomyopathy.
• The findings suggest FLNC variants can primarily impact the cardiac conduction system.

Implications:

• This case expands the known clinical spectrum of FLNC-related cardiomyopathies.
• FLNC variants should be considered in patients with unexplained cardiac conduction defects.
• Further research is needed to understand the specific mechanisms by which FLNC variants affect cardiac conduction.