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 language | English |
|---|---|
| Pages (from-to) | 1189-1194 |
| Number of pages | 6 |
| Journal | American Journal of Human Genetics |
| Volume | 71 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 1 2002 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Genetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10)
AU - Reid, Evan
AU - Kloos, Mark
AU - Ashley-Koch, Allison
AU - Hughes, Lori
AU - Bevan, Simon
AU - Svenson, Ingrid K.
AU - Graham, Felicia Lennon
AU - Gaskell, Perry C.
AU - Dearlove, Andrew
AU - Pericak-Vance, Margaret A
AU - Rubinsztein, David C.
AU - Marchuk, Douglas A.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=18644365196&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18644365196&partnerID=8YFLogxK
U2 - 10.1086/344210
DO - 10.1086/344210
M3 - Article
C2 - 12355402
AN - SCOPUS:18644365196
VL - 71
SP - 1189
EP - 1194
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 5
ER -