A case series of patients with filamin-C truncating variants attending a specialized cardiac genetic clinic.
Eur Heart J Case Rep
; 7(12): ytad572, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-38116480
ABSTRACT
Background:
FLNC encodes for filamin-C, a protein expressed in Z-discs of cardiac and skeletal muscle, involved in intracellular signalling and mechanical stabilization. Variants can cause diverse phenotypes with skeletal (myofibrillar or distal myopathy) and/or cardiac (hypertrophic, restrictive, and arrhythmogenic cardiomyopathies) manifestations. Truncating variants have recently been implicated in arrhythmogenic cardiomyopathy (ACM) without skeletal disease. Casesummary:
Retrospective review of medical records, including cardiac investigations, was performed for families attending a specialized clinic with a FLNC truncating variant (FLNCtv). Variants were classified according to accepted variant interpretation criteria. Of seven families identified, six had primary cardiac phenotypes with one nonsense and five frameshift variants (nonsense-mediated decay competent) identified. One family had no cardiac phenotype, with a pathogenic variant (p.Arg2467Alafs*62) identified as secondary genetic finding. Of the six with cardiac phenotypes, proband age at diagnosis ranged 27-35 years (four females). Five families experienced sudden cardiac death (SCD) of a young relative (age range 30-43 years), and one patient listed for cardiac transplant. Left ventricular (LV) ejection fraction ranged from 13 to 46%, with LV fibrosis (late gadolinium enhancement) on cardiac imaging or on postmortem histology seen in three families. Two families had one genotype-positive/phenotype-negative relative.Discussion:
The FLNCtv causes a left-sided ACM phenotype with a high risk of severe cardiac outcomes including end-stage heart failure and SCD. Incomplete penetrance is observed with implications for reporting secondary genetic findings.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Austrália