論文 - 詳細
| RRC ID | 19239 |
|---|---|
| 著者 | Kono S, Nishio T, Takahashi Y, Goto-Inoue N, Kinoshita M, Zaima N, Suzuki H, Fukutoku-Otsuji A, Setou M, Miyajima H. |
| タイトル | Dominant-negative effects of a novel mutation in the filamin myopathy. |
| ジャーナル | Neurology |
| Abstract |
BACKGROUND:Filamin myopathy is associated with mutations in the filamin C gene (FLNC) and is a myofibrillar myopathy characterized by focal myofibrillar destruction and cytoplasmic aggregates containing several Z-disk-related proteins. METHODS:This study investigated 6 Japanese patients with dominantly inherited myofibrillar myopathy manifested by adult-onset, slow and progressive muscle weakness and atrophy in the distal extremities. RESULTS:The abundantly expressed proteins in the affected muscles were identified as filamin C by nano liquid chromatography-tandem mass spectrometry. A genetic analysis of FLNC identified a heterozygous c.8107delG mutation that was localized to the dimerization domain of filamin C. A biochemical crosslinking analysis of bacterially expressed recombinant wild-type and mutant filamin C fragments demonstrated that the mutant monomer disturbed the proper dimerization of the wild-type filamin dimer, resulting in formation of a heterotrimer with the wild-type filamin dimer. The expression study in C2C12 myoblasts showed that the mutant filamin fragments formed cytoplasmic aggregates with endogenous wild-type filamin C. CONCLUSIONS:This study provides evidence for the dominant-negative effects of the FLNC mutation. These effects may be mutation-specific and likely result in the variation in the clinical phenotypes seen in patients with filamin myopathy. |
| 巻・号 | 75(6) |
| ページ | 547-54 |
| 公開日 | 2010-8-10 |
| DOI | 10.1212/WNL.0b013e3181ec7fbd |
| PII | 75/6/547 |
| PMID | 20697107 |
| MeSH | Adult Aged Amino Acid Sequence Animals Cell Line Contractile Proteins / genetics* Female Filamins Gene Deletion* Genes, Dominant / genetics* Genetic Carrier Screening Humans Male Mice Microfilament Proteins / genetics* Middle Aged Molecular Sequence Data Muscular Diseases / diagnosis* Muscular Diseases / genetics* Muscular Diseases / pathology Myoblasts / pathology Pedigree Phenotype |
| IF | 8.77 |
| 引用数 | 6 |
| WOS 分野 | CLINICAL NEUROLOGY |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |