Recently, a missense mutation (R7S) in yet another member of this family, HSPB3, was found to cause an axonal motor neuropathy (distal hereditary motor neuropathy type 2C, dHMN2C).
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 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.
The discovery of an HSPB3 mutation associated with an axonal motor neuropathy using a candidate gene approach supports the notion that the small heat shock protein gene family coordinately plays an important role in motor neuron viability.
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.