Myofibrillar myopathies

Selcen, Duygu

doi:10.1097/wco.0b013e32830a752b

Cited by 59 publications

(32 citation statements)

References 62 publications

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“…A recent study based on analysis of filamin C deficient mice indicated an important role for filamin C in muscle development and maintenance of muscle structural integrity [42]. Furthermore, mutations on the filamin C encoding gene have been implicated in myofibrillar myopathies leading to abnormal accumulation of an array of proteins at ectopic sites as well as accumulation of degraded myofibrillar proteins forming large aggregates and manifesting itself clinically in limb muscle weakness [43][44][45].…”

Section: Filamin and Cellular Organizationmentioning

confidence: 97%

Structural Portrait of Filamin Interaction Mechanisms

Djinović-Carugo¹,

Carugo

2010

CPPS

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We review the most recent findings on human filamin structure, with particular emphasis on the relationships between structure, function, and interaction. Filamin is a cytoskeletal actin-binding protein and it is therefore crucial in providing cells with the necessary mechanical and dynamical properties. Filamentous actin cross-linking by filamin is regulated by a number of other proteins and the molecular mechanisms of this complex interaction network can be understood by highlighting the structural features of isolated filamin moieties and of their complexes with several partners. Here we describe first the structure-function relationships of the isolated filamin, its flexibility, and its dimerization mechanism. Secondly, we illustrate the structural mechanism with which filamin can recognize its partners, both the actin filaments and the regulatory proteins.

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Section: Filamin and Cellular Organizationmentioning

confidence: 97%

Structural Portrait of Filamin Interaction Mechanisms

Djinović-Carugo¹,

Carugo

2010

CPPS

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“…This form of LGMD therefore overlaps with the myofibrillar myopathies, a group of diseases where the affected muscles may be distal, proximal or a mixture, with typically moderately raised serum CK (approximately five times the upper limit of normal) and characteristic histological features including vacuoles and accumulation of myofibrillar proteins such as desmin and myotilin. This histological appearance should prompt the search for mutations in the various genes responsible for the myofibrillar myopathies: desmin, myotilin, ZASP, alpha-beta crystallin and filamin C 9 10 11 12. There are similar pathological features in patients with valosin containing protein mutations where the clinical phenotype may include frontotemporal dementia and Paget’s disease of bone.…”

Section: Specific Types Of Limb Girdle Muscular Dystrophymentioning

confidence: 99%

Diagnosis and management of the limb girdle muscular dystrophies

Bushby

2009

Pract Neurol

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Making the diagnosis of a particular type of limb girdle muscular dystrophy (LGMD) can appear challenging. In fact, various clues from the way the patient presents, and the results of simple investigations such as creatine kinase levels, can be extremely helpful in sorting out the various disease entities within this group of patients. The results of more specialised testing of the muscle biopsy and DNA sequencing offer the prospect of a clear answer in around 75% of cases. As more is understood about the clinical features of the different types of LGMD, targeted management is increasingly possible, especially focusing on those patients at high risk of cardiac and respiratory complications.

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“…These are typical findings in myofibrillar myopathies (MFM), a clinically and genetically diverse group of progressive devastating hereditary skeletal and cardiac myopathies. Thus far MFM has been associated with mutations in seven genes ( DES, MYOT , LDB3 / ZASP , CRYAB , BAG3 , FLNC and FHL1 [33, 40–42]). Muscle biopsies from patients with the second filaminopathy variant show non-specific myopathic abnormalities without MFM pathology [6], while histological evaluation in cases with the intermediate variant indicated disease-associated myofibrillar abnormalities, but desmin-positive protein aggregates required for the diagnosis of MFM were not detected [18].…”

Section: Introductionmentioning

confidence: 99%

Filamin C-related myopathies: pathology and mechanisms

et al. 2012

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The term filaminopathy was introduced after a truncating mutation in the dimerization domain of filamin C (FLNc) was shown to be responsible for a devastating muscle disease. Subsequently, the same mutation was found in patients from diverse ethnical origins, indicating that this specific alteration is a mutational hot spot. Patients initially present with proximal muscle weakness, while distal and respiratory muscles become affected with disease progression. Muscle biopsies of these patients show typical signs of myofibrillar myopathy, including disintegration of myofibrils and aggregation of several proteins into distinct intracellular deposits. Highly similar phenotypes were observed in patients with other mutations in Ig-like domains of FLNc that result in expression of a noxious protein. Biochemical and biophysical studies showed that the mutated domains acquire an abnormal structure causing decreased stability and eventually becoming a seed for abnormal aggregation with other proteins. The disease usually presents only after the fourth decade of life possibly as a result of ageing-related impairments in the machinery that is responsible for disposal of damaged proteins. This is confirmed by mutations in components of this machinery that cause a highly similar phenotype. Transfection studies of cultured muscle cells reflect the events observed in patient muscles and, therefore, may provide a helpful model for testing future dedicated therapeutic strategies. More recently, FLNC mutations were also found in families with a distal myopathy phenotype, caused either by mutations in the actin-binding domain of FLNc that result in increased actin-binding and non-specific myopathic abnormalities without myofibrillar myopathy pathology, or a nonsense mutation in the rod domain that leads to RNA instability, haploinsufficiency with decreased expression levels of FLNc in the muscle fibers and myofibrillar abnormalities, but not to the formation of desmin-positive protein aggregates required for the diagnosis of myofibrillar myopathy.

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Myofibrillar myopathies

Cited by 59 publications

References 62 publications

Structural Portrait of Filamin Interaction Mechanisms

Structural Portrait of Filamin Interaction Mechanisms

Diagnosis and management of the limb girdle muscular dystrophies

Filamin C-related myopathies: pathology and mechanisms

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