The Z-Disk Diseases

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 642)


Recent studies have identified disease-causing mutations in four genes that encode Z-disk proteins. Mutations in myotilin (MYOT), ZASP and filamin C (FLNC) encoding genes cause autosomal dominant myopathy that manifests in adulthood. The clinical features and morphological changes in myopathies caused by mutations in all three genes are highly similar. The disease typically manifests as distal myopathy, but may also affect proximal muscles and the heart. The morphological findings are typical of myofibrillar myopathy (MFM) and include Z-disk alterations and aggregation of dense filamentous material visible in trichrome staining. The disease mechanism is still unclear, but may involve structural alterations of the Z-disk caused by dysfunctional proteins or their abnormal accumulation due to defective degradation. Although the fourth gene product, telethonin, is also involved in the Z-disk organization, its mutations cause a different phenotype. Telethonin mutations result in recessive muscular dystrophy, which manifests in childhood as proximal weakness. The morphologic alterations caused by telethonin mutations are not well characterized, but may share common features of MFM. Future work aims at understanding the pathophysiology of Z-disk related disorders and identification of novel genetic defects in patients with morphological features of MFM.


Muscular Dystrophy Sarcomeric Protein Muscle Specimen Distal Myopathy Variable Electron Density 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  1. 1.Department of Neurology, Division of Child Neurology and Neuromuscular Research Laboratory, Mayo ClinicCollege of MedicineRochesterUSA
  2. 2.Department of Pathology and Microbiology Division of PathologyUniversity of TurkuTurkuFinland
  3. 3.Turku University HospitalTurkuFinland

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