A novel heterozygous mutation in the C-terminal region of HSPB8 leads to limb-girdle rimmed vacuolar myopathy

Heat shock protein B8 (HspB8) is a small heat shock protein that plays a key role in preventing protein aggregation and facilitating turnover of damaged proteins in mechanically-strained tissues [1, 2]. Mutations in HSPB8 were initially found in distal hereditary motor neuropathy type IIa and Charcot-Marie-Tooth disease type 2L [3, 4]. More recently, HSPB8 variants were identified in rare myopathies with myofibrillar and rimmed vacuolar pathology, with or without an associated neuropathy [5 –8]. The discovery of such a phenotype was not surprising, as HspB8 is an integral player in chaperone-assisted selective autophagy, and mutations in other proteins involved in the same process, such as DNAJB6 and BAG3, can result in similar structural abnormalities [9, 10].

Source: Neuromuscular Disorders - February 10, 2020 Category: Neurology Authors: Stefan Nicolau, Teerin Liewluck, Jeffrey L Elliott, Andrew G Engel, Margherita Milone Source Type: research