Highlights
- •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
Abstract
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.
Keywords
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)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Mutations in the N-terminal actin-binding domain of Filamin C cause a distal myopathy.Am. J. Hum. Genet. 2011; https://doi.org/10.1016/j.ajhg.2011.04.021
- Filamin C plays an essential role in the maintenance of the structural integrity of cardiac and skeletal muscles, revealed by the medaka mutant zacro.Dev. Biol. 2012; https://doi.org/10.1016/j.ydbio.2011.10.008
- Filamin binds to the cytoplasmic domain of the beta1-integrin. Identification of amino acids responsible for this interaction.J. Biol. Chem. 1998; https://doi.org/10.1074/jbc.273.36.23304
- Filamin 2 (FLN2): a muscle-specific sarcoglycan interacting protein.J. Cell Biol. 2000; https://doi.org/10.1083/jcb.148.1.115
- Filamin C-related myopathies: pathology and mechanisms.Acta Neuropathol. 2013; https://doi.org/10.1007/s00401-012-1054-9
- Filamin C truncation mutations are associated with arrhythmogenic dilated cardiomyopathy and changes in the cell–cell adhesion structures.JACC Clin. Electrophysiol. 2018; https://doi.org/10.1016/j.jacep.2017.12.003
- Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients.Brain. 2007; https://doi.org/10.1093/brain/awm271
- Distal myopathy with upper limb predominance caused by Filamin C haploinsufficiency.Neurology. 2011; https://doi.org/10.1212/WNL.0b013e31823dc51e
- Widening the spectrum of Filamin-C myopathy: predominantly proximal myopathy due to the p.A193T mutation in the actin-binding domain of FLNC.Neuromuscul. Disord. 2017; https://doi.org/10.1016/j.nmd.2016.09.017
- A mutation in the dimerization domain of Filamin C causes a novel type of autosomal dominant myofibrillar myopathy.Am. J. Hum. Genet. 2005; (Web references: PyMOl: https://pymol.org)https://doi.org/10.1086/431959
Article info
Publication history
Published online: January 17, 2019
Accepted:
January 14,
2019
Received in revised form:
January 10,
2019
Received:
October 26,
2018
Identification
Copyright
© 2019 Published by Elsevier B.V.
