Mutations in small heat shock protein beta-1 (HspB1) have been linked to Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B.
So far disease causing mutations in HSPB1 have been associated with neurodegenerative diseases such as distal hereditary motor neuropathy, Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis.
Mutations in the <i>HSPB1</i> gene encoding the small heat shock protein B1 are associated with an autosomal dominant, axonal form of Charcot-Marie-Tooth disease 2F (CMT2F) and distal hereditary motor neuropathy.
Point mutants of HspB1 associated with distal hereditary motor neuropathy (G84R, L99M, R140G, K141Q, and P182S) were almost as effective as the wild-type HspB1 in modulation of NFL assembly.
To date, mutations in the coding regions of HSPB1 (Hsp27) and HSPB8 (Hsp22) were reported to cause distal hereditary motor neuropathy and Charcot-Marie-Tooth disease.
Mutations in the small heat-shock protein HSP27 gene are associated with distal hereditary motor neuropathy and with the axonal form of Charcot-Marie-Tooth disease type 2.
Mutations in the small heat shock protein HSPB1 (HSP27) are a cause of axonal Charcot-Marie-Tooth neuropathy (CMT2F) and distal hereditary motor neuropathy.
These observations suggest that overexpression of HSPB1(R136W) in neurons is sufficient to cause pathological and electrophysiological changes in mice that are seen in patients with hereditary motor neuropathy.
Mutations in the gene HSPB1, encoding the small heat shock protein 27 (HSP27), are a cause of distal hereditary motor neuropathy (dHMN) and axonal Charcot-Marie-Tooth disease (CMT2). dHMN and CMT2 are differentiated by the presence of a sensory neuropathy in the latter although in the case of HSPB1 this division is artificial as CMT2 secondary to HSPB1 mutations is predominantly a motor neuropathy with only minimal sensory involvement.
A number of missense mutations in the two related small heat shock proteins HspB8 (Hsp22) and HspB1 (Hsp27) have been associated with the inherited motor neuron diseases (MND) distal hereditary motor neuropathy and Charcot-Marie-Tooth disease.
We have previously shown that missense mutations in the small heat shock protein HSPB1 (HSP27) cause distal hereditary motor neuropathy and axonal Charcot-Marie-Tooth disease.
Thus, it has been demonstrated that mutation of either Hsp27 or the related protein hsp22 can be observed in specific families with hereditary motor neuropathy caused by premature axonal loss, possibly due to neuronal death and subsequent degeneration.