| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
a Human Molecular
Genetics Unit, School of Biochemistry and Genetics, University of
Newcastle upon Tyne, Newcastle upon Tyne NE2 4AA, UK, b Department of Neurology, Royal Victoria
Infirmary, Newcastle upon Tyne, UK, c Department of Neurology, Royal Manchester
Children's Hospital, Manchester, UK, d Department
of Medical Genetics, Wellcome Trust Centre for the Study of Molecular
Mechanisms in Disease, Wellcome/MRC Building, Addenbrooke's Hospital,
Cambridge, UK, e Department of Biological Sciences, University of
Durham, Durham, UK, f Department
of Developmental Biology, King's College, London, UK
Correspondence to: Dr Bushby, kate.bushby{at}ncl.ac.uk
Revised version received 10 May 2000;
Accepted for publication 20 June 2000
BACKGROUND
Hereditary spastic
paraparesis is a genetically heterogeneous condition. Recently,
mutations in the spastin gene were reported in families linked to the
common SPG4 locus on chromosome 2p21-22.
OBJECTIVESTo study a population of
patients with hereditary spastic paraparesis for mutations in the
spastin gene (SPG4) on chromosome 2p21-22.
METHODSDNA from 32 patients (12 from families known to be linked to SPG4)
was analysed for mutations in the spastin gene by single strand
conformational polymorphism analysis and sequencing. All patients were
also examined clinically.
RESULTSThirteen
SPG4 mutations were identified, 11 of which
are novel. These mutations include missense, nonsense, frameshift, and splice site mutations, the majority of which affect the AAA cassette. We also describe a nucleotide substitution outside this conserved region which appears to behave as a recessive mutation.
CONCLUSIONSRecurrent mutations in
the spastin gene are uncommon. This reduces the ease of mutation
detection as a part of the diagnostic work up of patients with
hereditary spastic paraparesis. Our findings have important
implications for the presumed function of spastin and schemes for
mutation detection in HSP patients.
This article has been cited by other articles:
|
|
 |
|
  A. Tarrade, C. Fassier, S. Courageot, D. Charvin, J. Vitte, L. Peris, A. Thorel, E. Mouisel, N. Fonknechten, N. Roblot, et al. A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition Hum. Mol. Genet., December 15, 2006; 15(24): 3544 - 3558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Beetz, A.O.H. Nygren, J. Schickel, M. Auer-Grumbach, K. Burk, G. Heide, J. Kassubek, S. Klimpe, T. Klopstock, F. Kreuz, et al. High frequency of partial SPAST deletions in autosomal dominant hereditary spastic paraplegia Neurology, December 12, 2006; 67(11): 1926 - 1930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Wood, J. A. Landers, M. Bingley, C. J. McDermott, V. Thomas-McArthur, L. J. Gleadall, P. J. Shaw, and V. T. Cunliffe The microtubule-severing protein Spastin is essential for axon outgrowth in the zebrafish embryo Hum. Mol. Genet., September 15, 2006; 15(18): 2763 - 2771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. McDermott, C. E. Burness, J. Kirby, L. E. Cox, D. G. Rao, C. Hewamadduma, B. Sharrack, M. Hadjivassiliou, P. F. Chinnery, A. Dalton, et al. Clinical features of hereditary spastic paraplegia due to spastin mutation. Neurology, July 11, 2006; 67(1): 45 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Depienne, C Tallaksen, J Y Lephay, B Bricka, S Poea-Guyon, B Fontaine, P Labauge, A Brice, and A Durr Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases J. Med. Genet., March 1, 2006; 43(3): 259 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Park, C.-S. Ki, H.-J. Kim, J.-W. Kim, D. H. Sung, B. J. Kim, and W. Y. Lee Mutation Analysis of SPG4 and SPG3A Genes and Its Implication in Molecular Diagnosis of Korean Patients With Hereditary Spastic Paraplegia Arch Neurol, July 1, 2005; 62(7): 1118 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Evans, E. R. Gomes, S. M. Reisenweber, G. G. Gundersen, and B. P. Lauring Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing J. Cell Biol., February 14, 2005; 168(4): 599 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yanase, K. Komai, T. Hamaguchi, S. Okino, H. Yokoji, T. Makifuchi, H. Takano, and M. Yamada Hereditary spastic paraplegia with frontal lobe dysfunction: A clinicopathologic study Neurology, December 14, 2004; 63(11): 2149 - 2152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Crone, N. T. Petersen, J. E. Nielsen, N. L. Hansen, and J. B. Nielsen Reciprocal inhibition and corticospinal transmission in the arm and leg in patients with autosomal dominant pure spastic paraparesis (ADPSP) Brain, December 1, 2004; 127(12): 2693 - 2702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Sellick, C. Longman, J. Tolmie, R. Newbury-Ecob, L. Geenhalgh, S. Hughes, M. Whiteford, C. Garrett, and R. S. Houlston Genomewide linkage searches for Mendelian disease loci can be efficiently conducted using high-density SNP genotyping arrays Nucleic Acids Res., November 23, 2004; 32(20): e164 - e164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Errico, P. Claudiani, M. D'Addio, and E. I. Rugarli Spastin interacts with the centrosomal protein NA14, and is enriched in the spindle pole, the midbody and the distal axon Hum. Mol. Genet., September 15, 2004; 13(18): 2121 - 2132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
August 24 Highlight and Commentary Neurology, August 24, 2004; 63(4): 603 - 603. [Full Text] [PDF]
|
|
|
|
|
|
P. F. Chinnery, S. M. Keers, M. J. Holden, V. Ramesh, and A. Dalton Infantile hereditary spastic paraparesis due to codominant mutations in the spastin gene Neurology, August 24, 2004; 63(4): 710 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Orlacchio, F. Gaudiello, A. Totaro, R. Floris, P. H. St George-Hyslop, G. Bernardi, and T. Kawarai A new SPG4 mutation in a variant form of spastic paraplegia with congenital arachnoid cysts Neurology, May 25, 2004; 62(10): 1875 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Molon, S. Di Giovanni, Y. W. Chen, P. M. Clarkson, C. Angelini, E. Pegoraro, and E. P. Hoffman Large-scale disruption of microtubule pathways in morphologically normal human spastin muscle Neurology, April 13, 2004; 62(7): 1097 - 1104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. McMonagle, P. Byrne, and M. Hutchinson Further evidence of dementia in SPG4-linked autosomal dominant hereditary spastic paraplegia Neurology, February 10, 2004; 62(3): 407 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Tang, G. Zhao, K. Xia, Q. Pan, W. Luo, L. Shen, Z. Long, H. Dai, X. Zi, and H. Jiang Three Novel Mutations of the Spastin Gene in Chinese Patients With Hereditary Spastic Paraplegia Arch Neurol, January 1, 2004; 61(1): 49 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A G Yip, A Durr, D A Marchuk, A Ashley-Koch, A Hentati, D C Rubinsztein, and E Reid Meta-analysis of age at onset in spastin-associated hereditary spastic paraplegia provides no evidence for a correlation with mutational class J. Med. Genet., September 1, 2003; 40(9): e106 - 106. [Full Text] [PDF]
|
|
|
|
 |
|
 D Bonsch, A Schwindt, P Navratil, D Palm, C Neumann, S Klimpe, J Schickel, J Hazan, C Weiller, T Deufel, et al. Motor system abnormalities in hereditary spastic paraparesis type 4 (SPG4) depend on the type of mutation in the spastin gene J. Neurol. Neurosurg. Psychiatry, August 1, 2003; 74(8): 1109 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Fink The Hereditary Spastic Paraplegias: Nine Genes and Counting Arch Neurol, August 1, 2003; 60(8): 1045 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. E. Tallaksen, E. Guichart-Gomez, P. Verpillat, V. Hahn-Barma, M. Ruberg, B. Fontaine, A. Brice, B. Dubois, and A. Durr Subtle Cognitive Impairment but No Dementia in Patients With Spastin Mutations Arch Neurol, August 1, 2003; 60(8): 1113 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E Reid Science in motion: common molecular pathological themes emerge in the hereditary spastic paraplegias J. Med. Genet., February 1, 2003; 40(2): 81 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Charvin, C. Cifuentes-Diaz, N. Fonknechten, V. Joshi, J. Hazan, J. Melki, and S. Betuing Mutations of SPG4 are responsible for a loss of function of spastin, an abundant neuronal protein localized in the nucleus Hum. Mol. Genet., January 1, 2003; 12(1): 71 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Starling, P Rocco, M R Passos-Bueno, J Hazan, S K Marie, and M Zatz Autosomal dominant (AD) pure spastic paraplegia (HSP) linked to locus SPG4 affects almost exclusively males in a large pedigree J. Med. Genet., December 1, 2002; 39(12): e77 - 77. [Full Text] [PDF]
|
|
|
|
|
|
I Yabe, H Sasaki, K Tashiro, T Matsuura, T Takegami, and T Satoh Spastin gene mutation in Japanese with hereditary spastic paraplegia J. Med. Genet., August 1, 2002; 39(8): e46 - 46. [Full Text] [PDF]
|
|
|
|
|
|
I. A. Meijer, C. K. Hand, P. Cossette, D. A. Figlewicz, and G. A. Rouleau Spectrum of SPG4 Mutations in a Large Collection of North American Families With Hereditary Spastic Paraplegia Arch Neurol, February 1, 2002; 59(2): 281 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Errico, A. Ballabio, and E. I. Rugarli Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics Hum. Mol. Genet., January 1, 2002; 11(2): 153 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S H Mead, C Proukakis, N Wood, A H Crosby, G T Plant, and T T Warner A large family with hereditary spastic paraparesis due to a frame shift mutation of the spastin (SPG4) gene: association with multiple sclerosis in two affected siblings and epilepsy in other affected family members J. Neurol. Neurosurg. Psychiatry, December 1, 2001; 71(6): 788 - 791. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
