Mutant small heat shock protein B3 causes motor neuropathy: utility of a candidate gene approach

Neurology. 2010 Feb 9;74(6):502-6. doi: 10.1212/WNL.0b013e3181cef84a.


Objective: Idiopathic peripheral neuropathy is common and likely due to genetic factors that are not detectable using standard linkage analysis. We initiated a candidate gene approach to study the genetic influence of the small heat shock protein (sHSP) gene family on an axonal motor and motor/sensory neuropathy patient population.

Methods: The promoter region and all exonic and intronic sequences of the 10 sHSP genes (HSPB1-HSPB10) were screened in a cohort of presumed nonacquired, axonal motor and motor/sensory neuropathy patients seen at the Ohio State University Neuromuscular Clinic.

Results: A missense mutation in the gene encoding small heat shock protein B3 (HSPB3, also called HSP27, protein 3) was discovered in 2 siblings with an asymmetric axonal motor neuropathy. Electrophysiologic studies revealed an axonal, predominantly motor, length-dependent neuropathy. The mutation, HSPB3(R7S), is located in the N-terminal domain and involves the loss of a conserved arginine.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • DNA Mutational Analysis / methods
  • Family Health
  • Female
  • Genetic Predisposition to Disease
  • Heat-Shock Proteins / genetics*
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Humans
  • Middle Aged
  • Mutation / genetics*
  • Pilot Projects


  • HSPB3 protein, human
  • Heat-Shock Proteins