1. The role of Z-disc proteins in myopathy and cardiomyopathy
- Author
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Katja Gehmlich, Kirsty Wadmore, and Amar J. Azad
- Subjects
0301 basic medicine ,myotilin ,Muscle Proteins ,Review ,Telethonin ,Biology ,Filamin ,Models, Biological ,Z-disc alternatively spliced PDZ-motif (ZASP) ,Sarcomere ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Muscular Diseases ,medicine ,Animals ,Humans ,Myotilin ,Myocyte ,Physical and Theoretical Chemistry ,Myopathy ,lcsh:QH301-705.5 ,telethonin ,Molecular Biology ,Spectroscopy ,Actin ,Organic Chemistry ,Skeletal muscle ,General Medicine ,missense variant ,truncating variant ,Computer Science Applications ,Cell biology ,myopalladin ,α-actinin 2 ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,lcsh:QD1-999 ,Mutation ,medicine.symptom ,Cardiomyopathies ,cardiomyopathy ,030217 neurology & neurosurgery ,filamin C ,myopathy - Abstract
The Z-disc acts as a protein-rich structure to tether thin filament in the contractile units, the sarcomeres, of striated muscle cells. Proteins found in the Z-disc are integral for maintaining the architecture of the sarcomere. They also enable it to function as a (bio-mechanical) signalling hub. Numerous proteins interact in the Z-disc to facilitate force transduction and intracellular signalling in both cardiac and skeletal muscle. This review will focus on six key Z-disc proteins: α-actinin 2, filamin C, myopalladin, myotilin, telethonin and Z-disc alternatively spliced PDZ-motif (ZASP), which have all been linked to myopathies and cardiomyopathies. We will summarise pathogenic variants identified in the six genes coding for these proteins and look at their involvement in myopathy and cardiomyopathy. Listing the Minor Allele Frequency (MAF) of these variants in the Genome Aggregation Database (GnomAD) version 3.1 will help to critically re-evaluate pathogenicity based on variant frequency in normal population cohorts.
- Published
- 2021