Asymmetrical late onset motor neuropathy associated with a novel mutation in the small heat shock protein HSPB1 (HSP27).
Distal hereditary motor neuropathy, also known as distal spinal muscular atrophy, is characterised by slowly progressive weakness and wasting of the hands and feet and has a heterogeneous genetic basis. One form of distal hereditary motor neuropathy is associated with mutations in the gene for the small heat shock protein HSPB1 (hsp27). Families have been described in which slowly progressive, symmetrical, lower limb predominant motor weakness is usually evident by middle age. Here we report a novel mutation, G84R, in an elderly patient presenting with strikingly asymmetrical weakness. Expression of this and other known mutations in cell culture demonstrated enhanced aggregation of mutant HSPB1 protein compared with wild-type.
James
P A
PA
MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Rankin
J
J
Talbot
K
K
D000368:Aged; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004568:Electrodiagnosis; D004576:Electromyography; D007839:Functional Laterality / Q000235:genetics*; D020233:Gait Disorders, Neurologic / Q000175:diagnosis / Q000235:genetics*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D018832:Molecular Chaperones; D016472:Motor Neuron Disease / Q000175:diagnosis / Q000235:genetics*; D018908:Muscle Weakness / Q000175:diagnosis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins