Format

Send to

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

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

Author information

1
Department of Neurology, The Ohio State University Medical Center, Hamilton Hall, Room 337B, 1645 Neil Ave., Columbus, OH 43210-1228, USA. stephen.kolb@osumc.edu

Abstract

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.

PMID:
20142617
DOI:
10.1212/WNL.0b013e3181cef84a
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center