- •Novel mutation in FLNC gene (c.A664G:p.M222V), within the N-terminal ABD domain
- •A predominant distal leg involvement and severe clinical course in FLNC mutation
- •Myofibrillar abnormalities and target fibers in distal myopathy due to FLNC mutation
Variants in Filamin C (FLNC) gene may cause either cardiomyopathies or different myopathies. We describe a family affected by a distal myopathy with autosomal dominant inheritance. The onset of the disease was in the third decade with gait impairment due to distal leg weakness. Subsequently, the disease progressed with an involvement of proximal lower limbs and hand muscles. Muscle biopsy, performed in one subject,identified relevant myofibrillar abnormalities.
We performed a target gene panel testing for myofibrillar myopathies by NGS approach which identified a novel mutation in exon 3 of FLNC gene (c.A664G:p.M222V), within the N-terminal actin-binding (ABD) domain. This variant has been identified in all affected members of the family, thus supporting its pathogenic role. Differently from previously identified variants, our family showed a predominant leg involvement and myofibrillar aggregates, thus further expanding the spectrum of Filamin C related myopathies.
Abbreviations:ABD (actin-binding domain), CMAP (compound muscle action potential), CK (creatine kinase), FLNC (Filamin C), EMG (electromyography), MUAP (motor unit action potential), NGS (Next Generation Sequencing)
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Published online: January 17, 2019
Accepted: January 14, 2019
Received in revised form: January 10, 2019
Received: October 26, 2018
© 2019 Published by Elsevier B.V.