A child with dilated cardiomyopathy and homozygous splice site variant in FLNC gene

FLNC gene encodes for Filamin-C (FLNC) protein, a sacromeric protein with important structural and signaling functions in the myocyte. Pathogenic dominant variants in FLNC were initially linked to myofibrillar myopathy and over time, evidence showed association of this gene with different forms of autosomal dominant cardiomyopathy including hypertrophic, dilated and restrictive forms. Recently, two cases of recessive FLNC mutations have been reported by Reinstein et al. and Kolbel et al., one with only cardiomyopathy and other with only myopathy. In this report, we describe a third case, a boy who was diagnosed at 10 years of age with shortness of breath and dilated cardiomyopathy who on sequencing was found to have a novel homozygous splice site variant (NM_001458.4 c.2122-1G>C) in FLNC. This case suggests that the phenotype associated with variants in FLNC is very heterogenous and can be inherited in dominant or recessive forms, with later being more severe and of earlier onset.

Automated summary

The FLNC gene encodes the Filamin-C (FLNC) protein, which plays important roles in structural and signaling functions in the myocyte. Pathogenic variations in FLNC have been associated with various forms of autosomal dominant cardiomyopathy. Recent reports have identified rare recessive FLNC mutations in individuals with either cardiomyopathy or myopathy. This suggests that the phenotypic expression of FLNC variants is highly heterogeneous and can be inherited in either dominant or recessive forms.