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In-frame deletion in the seventh immunoglobulin-like repeat of filamin C in a family with myofibrillar myopathy
- Source :
- European journal of human genetics : EJHG. 17(5)
- Publication Year :
- 2008
-
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.
- Subjects :
- Male
Filamins
DNA Mutational Analysis
Immunoblotting
Molecular Sequence Data
Immunoglobulins
macromolecular substances
Biology
medicine.disease_cause
Filamin
Article
03 medical and health sciences
0302 clinical medicine
Contractile Proteins
Muscular Diseases
Myofibrils
Genetics
medicine
Humans
FLNC
Amino Acid Sequence
Myopathy
Repeated sequence
Muscle, Skeletal
Gene
Peptide sequence
Genetics (clinical)
030304 developmental biology
Repetitive Sequences, Nucleic Acid
Sequence Deletion
Family Health
0303 health sciences
Mutation
Sequence Homology, Amino Acid
Microfilament Proteins
medicine.disease
Molecular biology
Immunohistochemistry
3. Good health
Microscopy, Electron
Female
medicine.symptom
030217 neurology & neurosurgery
Limb-girdle muscular dystrophy
Subjects
Details
- ISSN :
- 14765438
- Volume :
- 17
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- European journal of human genetics : EJHG
- Accession number :
- edsair.doi.dedup.....89f102cd786cbab19fc03e3075e2cd48