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September 27, 2004

Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary spastic paraplegia

September 28, 2004 issue
63 (6) 1108-1110

Abstract

Hereditary spastic paraplegias (HSPs) are characterized by progressive lower extremity spasticity due to an axonal degeneration of motor and sensory neurons. We report a four-generation pedigree segregating an autosomal dominant phenotype for HSP and showing a linkage to the SPG10 locus, coding for Kinesin family member 5A. Subsequent to a denaturing high performance liquid chromatography (dHPLC) mutation screening we found a new missense mutation 838C>T (R280C) at an invariant arginine residue in a region involved in the microtubule binding activity.

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References

1.
McDermott C, White K, Bushby K, Shaw P. Hereditary spastic paraparesis: a review of new developments. J Neurol Neurosurg Psychiatry. 2000; 69: 150–60.
2.
Reid E. Science in motion: common molecular pathological themes emerge in the hereditary spastic paraplegias. J Med Genet. 2003; 40: 81–86.
3.
Errico A, Ballabio A, Rugarli EI. Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics. Hum Mol Genet. 2002; 11: 153–163.
4.
Reid E, Kloos M, Ashley-Koch A, et al. A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). Am J Hum Genet. 2002; 71: 1189–1194.
5.
Reid E, Dearlove AM, Rhodes M, Rubinsztein C. A new locus for autosomal dominant “pure” hereditary spastic paraplegia mapping to chromosome 12q13, and evidence for further genetic heterogeneity. Am J Hum Genet. 1999; 65: 757–763.
6.
Xia CH, Roberts EA, Her LS, et al. Abnormal neurofilament transport caused by targeted disruption of kinesin heavy chain KIF5A. J Cell Biol. 2003; 161: 55–66.
7.
Kikkawa M, Sablin EP, Okada Y, Yajima H, Fletterick RJ, Hirokawa N. Switch-based mechanism of kinesin motors. Nature. 2001; 411: 439–445.
8.
Hoenger A, Thormahlen M, Diaz-Avalos R, et al. A new look at the microtubule binding patterns of dimeric kinesins. J Mol Biol. 2000; 297: 1087–103.
9.
Woehlke G, Ruby AK, Hart CL, Ly B, Hom-Booher N, Vale RD. Microtubule interaction site of the kinesin motor. Cell. 1997; 90: 207–216.
10.
Wilkie AO. The molecular basis of genetic dominance. J Med Genet. 1994; 31: 89–98.

Information & Authors

Information

Published In

Neurology®
Volume 63Number 6September 28, 2004
Pages: 1108-1110
PubMed: 15452312

Publication History

Received: March 4, 2004
Accepted: May 13, 2004
Published online: September 27, 2004
Published in print: September 28, 2004

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Authors

Affiliations & Disclosures

M. Fichera, PhD
From Genetic Diagnostic Laboratory (Drs. Fichera, Lo Giudice, Falco, Sturnio, Amata), IRCCS Oasi M. SS. Troina, Italy; Department of Experimental Medicine and Diagnostics, Medical Genetics Service (Drs. Calabrese, Bigoni, Calzolari, Neri), University of Ferrara, Ferrara, Italy.
M. Lo Giudice, BS
From Genetic Diagnostic Laboratory (Drs. Fichera, Lo Giudice, Falco, Sturnio, Amata), IRCCS Oasi M. SS. Troina, Italy; Department of Experimental Medicine and Diagnostics, Medical Genetics Service (Drs. Calabrese, Bigoni, Calzolari, Neri), University of Ferrara, Ferrara, Italy.
M. Falco, BS
From Genetic Diagnostic Laboratory (Drs. Fichera, Lo Giudice, Falco, Sturnio, Amata), IRCCS Oasi M. SS. Troina, Italy; Department of Experimental Medicine and Diagnostics, Medical Genetics Service (Drs. Calabrese, Bigoni, Calzolari, Neri), University of Ferrara, Ferrara, Italy.
M. Sturnio, BS
From Genetic Diagnostic Laboratory (Drs. Fichera, Lo Giudice, Falco, Sturnio, Amata), IRCCS Oasi M. SS. Troina, Italy; Department of Experimental Medicine and Diagnostics, Medical Genetics Service (Drs. Calabrese, Bigoni, Calzolari, Neri), University of Ferrara, Ferrara, Italy.
S. Amata, BS
From Genetic Diagnostic Laboratory (Drs. Fichera, Lo Giudice, Falco, Sturnio, Amata), IRCCS Oasi M. SS. Troina, Italy; Department of Experimental Medicine and Diagnostics, Medical Genetics Service (Drs. Calabrese, Bigoni, Calzolari, Neri), University of Ferrara, Ferrara, Italy.
O. Calabrese, MD
From Genetic Diagnostic Laboratory (Drs. Fichera, Lo Giudice, Falco, Sturnio, Amata), IRCCS Oasi M. SS. Troina, Italy; Department of Experimental Medicine and Diagnostics, Medical Genetics Service (Drs. Calabrese, Bigoni, Calzolari, Neri), University of Ferrara, Ferrara, Italy.
S. Bigoni, MD
From Genetic Diagnostic Laboratory (Drs. Fichera, Lo Giudice, Falco, Sturnio, Amata), IRCCS Oasi M. SS. Troina, Italy; Department of Experimental Medicine and Diagnostics, Medical Genetics Service (Drs. Calabrese, Bigoni, Calzolari, Neri), University of Ferrara, Ferrara, Italy.
E. Calzolari, MD
From Genetic Diagnostic Laboratory (Drs. Fichera, Lo Giudice, Falco, Sturnio, Amata), IRCCS Oasi M. SS. Troina, Italy; Department of Experimental Medicine and Diagnostics, Medical Genetics Service (Drs. Calabrese, Bigoni, Calzolari, Neri), University of Ferrara, Ferrara, Italy.
M. Neri, MD
From Genetic Diagnostic Laboratory (Drs. Fichera, Lo Giudice, Falco, Sturnio, Amata), IRCCS Oasi M. SS. Troina, Italy; Department of Experimental Medicine and Diagnostics, Medical Genetics Service (Drs. Calabrese, Bigoni, Calzolari, Neri), University of Ferrara, Ferrara, Italy.

Notes

Address correspondence and reprint requests to Dr. Marco Fichera, Laboratorio di Diagnosi Genetica, IRCCS Oasi Maria SS., via Conte Ruggero 73, 94018 Troina (EN) Italy; e-mail: [email protected]

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