In-frame deletion in the seventh immunoglobulin-like repeat of filamin C in a family with myofibrillar myopathy
Open Access
- 3 December 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in European Journal of Human Genetics
- Vol. 17 (5), 656-663
- https://doi.org/10.1038/ejhg.2008.226
Abstract
Myofibrillar myopathies (MFMs) are an expanding and increasingly recognized group of neuromuscular disorders caused by mutations in DES, CRYAB, MYOT, and ZASP. The latest gene to be associated with MFM was FLNC; a p.W2710X mutation in the 24th immunoglobulin-like repeat of filamin C was shown to be the cause of a distinct type of MFM in several German families. We studied an International cohort of 46 patients from 39 families with clinically and myopathologically confirmed MFM, in which DES, CRYAB, MYOT, and ZASP mutations have been excluded. In patients from an unrelated family a 12-nucleotide deletion (c.2997_3008del) in FLNC resulting in a predicted in-frame four-residue deletion (p.Val930_Thr933del) in the seventh repeat of filamin C was identified. Both affected family members, mother and daughter, but not unrelated control individuals, carried the p.Val930_Thr933del mutation. The mutation is transcribed and, based on myopathological features and immunoblot analysis, it leads to an accumulation of dysfunctional filamin C in the myocytes. The study results suggest that the novel p.Val930_Thr933del mutation in filamin C is the cause of MFM but also indicate that filamin C mutations are a comparatively rare cause of MFM.Keywords
This publication has 23 references indexed in Scilit:
- Electron microscopy in myofibrillar myopathies reveals clues to the mutated geneNeuromuscular Disorders, 2008
- Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patientsBrain, 2004
- Section: Cytoskeletal Proteins; Mechanical response of single filamin A (ABP-280) molecules and its role in the actin cytoskeletonJournal of Muscle Research and Cell Motility, 2002
- Mechanical unfolding of single filamin A (ABP‐280) molecules detected by atomic force microscopyFEBS Letters, 2001
- Structural and functional aspects of filaminsBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2001
- Filamins as integrators of cell mechanics and signallingNature Reviews Molecular Cell Biology, 2001
- FATZ, a Filamin-, Actinin-, and Telethonin-binding Protein of the Z-disc of Skeletal MusclePublished by Elsevier BV ,2000
- Desmin Myopathy, a Skeletal Myopathy with Cardiomyopathy Caused by Mutations in the Desmin GeneNew England Journal of Medicine, 2000
- Characterization of muscle filamin isoforms suggests a possible role of ?-filamin/ABP-L in sarcomeric Z-disc formationCell Motility, 2000
- Myofibrillar myopathyAnnals of Neurology, 1999