This study provides novel information on the molecular pathway underlying the HSPB5 physiological function in skeletal muscle, confirming the contribution of the pro-oxidant environment in HSPB5 activation and interaction with substrate/client myofibrillar proteins, offering new insights for the study of myofibrillar myopathies and cardiomyopathies.
This study aimed to investigate the pathological mechanisms involved in an early-onset myofibrillar myopathy manifesting in a child harboring a homozygous recessive mutation in HSPB5, 343delT.
Dependent on the MFM causing mutation, different sets of proteins were revealed as genuine (accumulated) plaque components in independent technical replicates: (i) αB-crystallin, desmin, filamin A/C, myotilin, PRAF3, RTN2, SQSTM, XIRP1, and XIRP2 (patient with defined MFM mutation distinct from FHL1) or (ii) desmin, FHL1, filamin A/C, KBTBD10, NRAP, SQSTM, RL40, XIRP1, and XIRP2 (patient with FHL1 mutation).
Myofibrillar myopathies (MFM) are a group of disorders associated with mutations in DES, CRYAB, MYOT, ZASP, FLNC, or BAG3 genes and characterized by disintegration of myofibrils and accumulation of degradation products into intracellular inclusions.
Myofibrillar myopathies (MFMs) are an expanding and increasingly recognized group of neuromuscular disorders caused by mutations in DES, CRYAB, MYOT, and ZASP.