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

Evan Reid, Mark Kloos, Allison Ashley-Koch, Lori Hughes, Simon Bevan, Ingrid K. Svenson, Felicia Lennon Graham, Perry C. Gaskell, Andrew Dearlove, Margaret A Pericak-Vance, David C. Rubinsztein, Douglas A. Marchuk

Research output: Contribution to journalArticle

354 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1189-1194
Number of pages6
JournalAmerican Journal of Human Genetics
Volume71
Issue number5
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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Hereditary Spastic Paraplegia
Kinesin
Mutation
Axons
Axonal Transport
Asparagine
Missense Mutation
Microtubules
Organelles
Adenosine Triphosphatases
Central Nervous System
Pathology
Phenotype
Genes
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Reid, E., Kloos, M., Ashley-Koch, A., Hughes, L., Bevan, S., Svenson, I. K., ... Marchuk, D. A. (2002). A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). American Journal of Human Genetics, 71(5), 1189-1194. https://doi.org/10.1086/344210

A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). / Reid, Evan; Kloos, Mark; Ashley-Koch, Allison; Hughes, Lori; Bevan, Simon; Svenson, Ingrid K.; Graham, Felicia Lennon; Gaskell, Perry C.; Dearlove, Andrew; Pericak-Vance, Margaret A; Rubinsztein, David C.; Marchuk, Douglas A.

In: American Journal of Human Genetics, Vol. 71, No. 5, 01.11.2002, p. 1189-1194.

Research output: Contribution to journalArticle

Reid, E, Kloos, M, Ashley-Koch, A, Hughes, L, Bevan, S, Svenson, IK, Graham, FL, Gaskell, PC, Dearlove, A, Pericak-Vance, MA, Rubinsztein, DC & Marchuk, DA 2002, 'A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10)', American Journal of Human Genetics, vol. 71, no. 5, pp. 1189-1194. https://doi.org/10.1086/344210
Reid E, Kloos M, Ashley-Koch A, Hughes L, Bevan S, Svenson IK et al. A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). American Journal of Human Genetics. 2002 Nov 1;71(5):1189-1194. https://doi.org/10.1086/344210
Reid, Evan ; Kloos, Mark ; Ashley-Koch, Allison ; Hughes, Lori ; Bevan, Simon ; Svenson, Ingrid K. ; Graham, Felicia Lennon ; Gaskell, Perry C. ; Dearlove, Andrew ; Pericak-Vance, Margaret A ; Rubinsztein, David C. ; Marchuk, Douglas A. / A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). In: American Journal of Human Genetics. 2002 ; Vol. 71, No. 5. pp. 1189-1194.
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