In this study, we modeled HSPB1 mutant-induced neuropathies in Drosophila using a human HSPB1<sup>S135F</sup> mutant that has a missense mutation in its α-crystallin domain.
This review extensively profiles the published literature on CMT2F and distal hereditary motor neuropathy II (dHMN II), a similar neuropathy with exclusively motor symptoms that is also due to mutations in Hsp27.
A detailed phenotype and natural history study of HSPB1neuropathy is therefore required in order to inform the duration and outcome measures of any future trials.
Together, these findings suggest that the mitochondrial abnormalities in mutant Hsp27-induced neuropathies may be a primary cause of pathology, leading to further deficits in the mitochondrial axonal transport and onset of disease.
Physico-chemical properties of the mutations G34R, P39L and E41K in the N-terminal domain of human heat shock protein B1 (HspB1), which have been associated with hereditary motor neuron neuropathy, were analyzed.
Mutations in the small heat shock protein HSPB1 (HSP27) are a cause of axonal Charcot-Marie-Tooth neuropathy (CMT2F) and distal hereditary motor neuropathy.
However, we present a family with a novel mutation in the C-terminus of HSP27 (p.Gln175X) [corrected] with a motor predominant distal neuropathy but with definite sensory involvement compatible with CMT2.