Truncated HSPB1 causes axonal neuropathy and impairs tolerance to unfolded protein stress.

ABSTRACT:

Background

HSPB1 belongs to the family of small heat shock proteins (sHSP) that have importance in protection against unfolded protein stress, in cancer cells for escaping drug toxicity stress and in neurons for suppression of protein aggregates. sHSPs have a conserved α-crystalline domain (ACD), flanked by variable N- and C-termini, whose functions are not fully understood. Dominant missense variants in HSPB1, locating mostly to the ACD, have been linked to inherited neuropathy.

Methods

Patients underwent detailed clinical and neurophysiologic characterization. Disease causing variants were identified by exome or gene panel sequencing. Primary patient fibroblasts were used to investigate the effects of the dominant defective HSPB1 proteins.

Results

Frameshift variant

SUBMITTER: Ylikallio E 

PROVIDER: S-EPMC4661565 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature