A Mutation in the Dimerization Domain of Filamin C Causes a Novel Type of Autosomal Dominant Myofibrillar Myopathy
AUTOR(ES)
Vorgerd, Matthias
FONTE
The American Society of Human Genetics
RESUMO
Myofibrillar myopathy (MFM) is a human disease that is characterized by focal myofibrillar destruction and pathological cytoplasmic protein aggregations. In an extended German pedigree with a novel form of MFM characterized by clinical features of a limb-girdle myopathy and morphological features of MFM, we identified a cosegregating, heterozygous nonsense mutation (8130G→A; W2710X) in the filamin c gene (FLNC) on chromosome 7q32.1. The mutation is the first found in FLNC and is localized in the dimerization domain of filamin c. Functional studies showed that, in the truncated mutant protein, this domain has a disturbed secondary structure that leads to the inability to dimerize properly. As a consequence of this malfunction, the muscle fibers of our patients display massive cytoplasmic aggregates containing filamin c and several Z-disk–associated and sarcolemmal proteins.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1224531Documentos Relacionados
- A mutation in the alpha 3 chain of type IX collagen causes autosomal dominant multiple epiphyseal dysplasia with mild myopathy
- Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis.
- A novel G21R mutation of the GJB2 gene causes autosomal dominant non-syndromic congenital deafness in a Cuban family
- Autosomal dominant myopathy: Missense mutation (Glu-706 → Lys) in the myosin heavy chain IIa gene
- c.G2114A MYH9 mutation (DFNA17) causes non-syndromic autosomal dominant hearing loss in a Brazilian family