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Am J Hum Genet. 2002 Nov;71(5):1189-94. Epub 2002 Sep 24.

A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10).

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  • 1Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, United Kingdom. ereid@hgmp.mrc.ac.uk

Abstract

We have identified a missense mutation in the motor domain of the neuronal kinesin heavy chain gene KIF5A, in a family with hereditary spastic paraplegia. The mutation occurs in the family in which the SPG10 locus was originally identified, at an invariant asparagine residue that, when mutated in orthologous kinesin heavy chain motor proteins, prevents stimulation of the motor ATPase by microtubule-binding. Mutation of kinesin orthologues in various species leads to phenotypes resembling hereditary spastic paraplegia. The conventional kinesin motor powers intracellular movement of membranous organelles and other macromolecular cargo from the neuronal cell body to the distal tip of the axon. This finding suggests that the underlying pathology of SPG10 and possibly of other forms of hereditary spastic paraplegia may involve perturbation of neuronal anterograde (or retrograde) axoplasmic flow, leading to axonal degeneration, especially in the longest axons of the central nervous system.

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PMID:
12355402
[PubMed - indexed for MEDLINE]
PMCID:
PMC385095
Free PMC Article

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