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J Med Genet. Feb 2003; 40(2): 81–86.
PMCID: PMC1735361

Science in motion: common molecular pathological themes emerge in the hereditary spastic paraplegias

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Selected References

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  • Harding AE. Hereditary spastic paraplegias. Semin Neurol. 1993 Dec;13(4):333–336. [PubMed]
  • Fink JK, Heiman-Patterson T, Bird T, Cambi F, Dubé MP, Figlewicz DA, Fink JK, Haines JL, Heiman-Patterson T, Hentati A, et al. Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group. Neurology. 1996 Jun;46(6):1507–1514. [PubMed]
  • Reid E. Pure hereditary spastic paraplegia. J Med Genet. 1997 Jun;34(6):499–503. [PMC free article] [PubMed]
  • Reid E. The hereditary spastic paraplegias. J Neurol. 1999 Nov;246(11):995–1003. [PubMed]
  • Jouet M, Rosenthal A, Armstrong G, MacFarlane J, Stevenson R, Paterson J, Metzenberg A, Ionasescu V, Temple K, Kenwrick S. X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nat Genet. 1994 Jul;7(3):402–407. [PubMed]
  • Tamagaki A, Shima M, Tomita R, Okumura M, Shibata M, Morichika S, Kurahashi H, Giddings JC, Yoshioka A, Yokobayashi Y. Segregation of a pure form of spastic paraplegia and NOR insertion into Xq11.2. Am J Med Genet. 2000 Sep 4;94(1):5–8. [PubMed]
  • Hazan J, Lamy C, Melki J, Munnich A, de Recondo J, Weissenbach J. Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. Nat Genet. 1993 Oct;5(2):163–167. [PubMed]
  • Zhao X, Alvarado D, Rainier S, Lemons R, Hedera P, Weber CH, Tukel T, Apak M, Heiman-Patterson T, Ming L, et al. Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nat Genet. 2001 Nov;29(3):326–331. [PubMed]
  • Hazan J, Fontaine B, Bruyn RP, Lamy C, van Deutekom JC, Rime CS, Dürr A, Melki J, Lyon-Caen O, Agid Y, et al. Linkage of a new locus for autosomal dominant familial spastic paraplegia to chromosome 2p. Hum Mol Genet. 1994 Sep;3(9):1569–1573. [PubMed]
  • Hazan J, Fonknechten N, Mavel D, Paternotte C, Samson D, Artiguenave F, Davoine CS, Cruaud C, Dürr A, Wincker P, et al. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat Genet. 1999 Nov;23(3):296–303. [PubMed]
  • Fink JK, Wu CT, Jones SM, Sharp GB, Lange BM, Lesicki A, Reinglass T, Varvil T, Otterud B, Leppert M. Autosomal dominant familial spastic paraplegia: tight linkage to chromosome 15q. Am J Hum Genet. 1995 Jan;56(1):188–192. [PMC free article] [PubMed]
  • Hedera P, Rainier S, Alvarado D, Zhao X, Williamson J, Otterud B, Leppert M, Fink JK. Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q. Am J Hum Genet. 1999 Feb;64(2):563–569. [PMC free article] [PubMed]
  • Reid E, Dearlove AM, Whiteford ML, Rhodes M, Rubinsztein DC. Autosomal dominant spastic paraplegia: refined SPG8 locus and additional genetic heterogeneity. Neurology. 1999 Nov 10;53(8):1844–1849. [PubMed]
  • Seri M, Cusano R, Forabosco P, Cinti R, Caroli F, Picco P, Bini R, Morra VB, De Michele G, Lerone M, et al. Genetic mapping to 10q23.3-q24.2, in a large Italian pedigree, of a new syndrome showing bilateral cataracts, gastroesophageal reflux, and spastic paraparesis with amyotrophy. Am J Hum Genet. 1999 Feb;64(2):586–593. [PMC free article] [PubMed]
  • Reid E, Dearlove AM, Rhodes M, Rubinsztein DC. 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 Sep;65(3):757–763. [PMC free article] [PubMed]
  • 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, et al. A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). Am J Hum Genet. 2002 Nov;71(5):1189–1194. [PMC free article] [PubMed]
  • Reid E, Dearlove AM, Osborn O, Rogers MT, Rubinsztein DC. A locus for autosomal dominant "pure" hereditary spastic paraplegia maps to chromosome 19q13. Am J Hum Genet. 2000 Feb;66(2):728–732. [PMC free article] [PubMed]
  • Fontaine B, Davoine CS, Dürr A, Paternotte C, Feki I, Weissenbach J, Hazan J, Brice A. A new locus for autosomal dominant pure spastic paraplegia, on chromosome 2q24-q34. Am J Hum Genet. 2000 Feb;66(2):702–707. [PMC free article] [PubMed]
  • Hansen Jens Jacob, Dürr Alexandra, Cournu-Rebeix Isabelle, Georgopoulos Costa, Ang Debbie, Nielsen Marit Nyholm, Davoine Claire-Sophie, Brice Alexis, Fontaine Bertrand, Gregersen Niels, et al. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am J Hum Genet. 2002 May;70(5):1328–1332. [PMC free article] [PubMed]
  • Patel H, Hart PE, Warner TT, Houlston RS, Patton MA, Jeffery S, Crosby AH. The Silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype. Am J Hum Genet. 2001 Jul;69(1):209–215. [PMC free article] [PubMed]
  • Valente Enza Maria, Brancati Francesco, Caputo Viviana, Bertini Enrico, Patrono Clarice, Costanti Danilo, Dallapiccola Bruno. Novel locus for autosomal dominant pure hereditary spastic paraplegia (SPG19) maps to chromosome 9q33-q34. Ann Neurol. 2002 Jun;51(6):681–685. [PubMed]
  • Hentati A, Pericak-Vance MA, Hung WY, Belal S, Laing N, Boustany RM, Hentati F, Ben Hamida M, Siddique T. Linkage of 'pure' autosomal recessive familial spastic paraplegia to chromosome 8 markers and evidence of genetic locus heterogeneity. Hum Mol Genet. 1994 Aug;3(8):1263–1267. [PubMed]
  • De Michele G, De Fusco M, Cavalcanti F, Filla A, Marconi R, Volpe G, Monticelli A, Ballabio A, Casari G, Cocozza S. A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3. Am J Hum Genet. 1998 Jul;63(1):135–139. [PMC free article] [PubMed]
  • Casari G, De Fusco M, Ciarmatori S, Zeviani M, Mora M, Fernandez P, De Michele G, Filla A, Cocozza S, Marconi R, et al. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell. 1998 Jun 12;93(6):973–983. [PubMed]
  • Martínez Murillo F, Kobayashi H, Pegoraro E, Galluzzi G, Creel G, Mariani C, Farina E, Ricci E, Alfonso G, Pauli RM, et al. Genetic localization of a new locus for recessive familial spastic paraparesis to 15q13-15. Neurology. 1999 Jul 13;53(1):50–56. [PubMed]
  • Vazza G, Zortea M, Boaretto F, Micaglio GF, Sartori V, Mostacciuolo ML. A new locus for autosomal recessive spastic paraplegia associated with mental retardation and distal motor neuropathy, SPG14, maps to chromosome 3q27-q28. Am J Hum Genet. 2000 Aug;67(2):504–509. [PMC free article] [PubMed]
  • Hughes CA, Byrne PC, Webb S, McMonagle P, Patterson V, Hutchinson M, Parfrey NA. SPG15, a new locus for autosomal recessive complicated HSP on chromosome 14q. Neurology. 2001 May 8;56(9):1230–1233. [PubMed]
  • Patel Heema, Cross Harold, Proukakis Christos, Hershberger Ruth, Bork Peer, Ciccarelli Francesca D, Patton Michael A, McKusick Victor A, Crosby Andrew H. SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nat Genet. 2002 Aug;31(4):347–348. [PubMed]
  • Jouet M, Moncla A, Paterson J, McKeown C, Fryer A, Carpenter N, Holmberg E, Wadelius C, Kenwrick S. New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome. Am J Hum Genet. 1995 Jun;56(6):1304–1314. [PMC free article] [PubMed]
  • Kenwrick S, Watkins A, De Angelis E. Neural cell recognition molecule L1: relating biological complexity to human disease mutations. Hum Mol Genet. 2000 Apr 12;9(6):879–886. [PubMed]
  • Lemmon V, Farr KL, Lagenaur C. L1-mediated axon outgrowth occurs via a homophilic binding mechanism. Neuron. 1989 Jun;2(6):1597–1603. [PubMed]
  • Kunz S, Spirig M, Ginsburg C, Buchstaller A, Berger P, Lanz R, Rader C, Vogt L, Kunz B, Sonderegger P. Neurite fasciculation mediated by complexes of axonin-1 and Ng cell adhesion molecule. J Cell Biol. 1998 Dec 14;143(6):1673–1690. [PMC free article] [PubMed]
  • Dahme M, Bartsch U, Martini R, Anliker B, Schachner M, Mantei N. Disruption of the mouse L1 gene leads to malformations of the nervous system. Nat Genet. 1997 Nov;17(3):346–349. [PubMed]
  • Fransen E, D'Hooge R, Van Camp G, Verhoye M, Sijbers J, Reyniers E, Soriano P, Kamiguchi H, Willemsen R, Koekkoek SK, et al. L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns. Hum Mol Genet. 1998 Jun;7(6):999–1009. [PubMed]
  • Gencic S, Abuelo D, Ambler M, Hudson LD. Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein. Am J Hum Genet. 1989 Sep;45(3):435–442. [PMC free article] [PubMed]
  • Hudson LD, Puckett C, Berndt J, Chan J, Gencic S. Mutation of the proteolipid protein gene PLP in a human X chromosome-linked myelin disorder. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8128–8131. [PMC free article] [PubMed]
  • Cambi F, Tang XM, Cordray P, Fain PR, Keppen LD, Barker DF. Refined genetic mapping and proteolipid protein mutation analysis in X-linked pure hereditary spastic paraplegia. Neurology. 1996 Apr;46(4):1112–1117. [PubMed]
  • Sivakumar K, Sambuughin N, Selenge B, Nagle JW, Baasanjav D, Hudson LD, Goldfarb LG. Novel exon 3B proteolipid protein gene mutation causing late-onset spastic paraplegia type 2 with variable penetrance in female family members. Ann Neurol. 1999 May;45(5):680–683. [PubMed]
  • Mimault C, Giraud G, Courtois V, Cailloux F, Boire JY, Dastugue B, Boespflug-Tanguy O. Proteolipoprotein gene analysis in 82 patients with sporadic Pelizaeus-Merzbacher Disease: duplications, the major cause of the disease, originate more frequently in male germ cells, but point mutations do not. The Clinical European Network on Brain Dysmyelinating Disease. Am J Hum Genet. 1999 Aug;65(2):360–369. [PMC free article] [PubMed]
  • Ellis D, Malcolm S. Proteolipid protein gene dosage effect in Pelizaeus-Merzbacher disease. Nat Genet. 1994 Apr;6(4):333–334. [PubMed]
  • Yool DA, Edgar JM, Montague P, Malcolm S. The proteolipid protein gene and myelin disorders in man and animal models. Hum Mol Genet. 2000 Apr 12;9(6):987–992. [PubMed]
  • Cailloux F, Gauthier-Barichard F, Mimault C, Isabelle V, Courtois V, Giraud G, Dastugue B, Boespflug-Tanguy O. Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating Disease. Eur J Hum Genet. 2000 Nov;8(11):837–845. [PubMed]
  • Griffiths IR, Montague P, Dickinson P. The proteolipid protein gene. Neuropathol Appl Neurobiol. 1995 Apr;21(2):85–96. [PubMed]
  • Cambi F, Tartaglino L, Lublin F, McCarren D. X-linked pure familial spastic paraparesis. Characterization of a large kindred with magnetic resonance imaging studies. Arch Neurol. 1995 Jul;52(7):665–669. [PubMed]
  • Kobayashi H, Hoffman EP, Marks HG. The rumpshaker mutation in spastic paraplegia. Nat Genet. 1994 Jul;7(3):351–352. [PubMed]
  • Confalonieri F, Duguet M. A 200-amino acid ATPase module in search of a basic function. Bioessays. 1995 Jul;17(7):639–650. [PubMed]
  • Beyer A. Sequence analysis of the AAA protein family. Protein Sci. 1997 Oct;6(10):2043–2058. [PMC free article] [PubMed]
  • Patel S, Latterich M. The AAA team: related ATPases with diverse functions. Trends Cell Biol. 1998 Feb;8(2):65–71. [PubMed]
  • Arlt H, Tauer R, Feldmann H, Neupert W, Langer T. The YTA10-12 complex, an AAA protease with chaperone-like activity in the inner membrane of mitochondria. Cell. 1996 Jun 14;85(6):875–885. [PubMed]
  • Leonhard K, Stiegler A, Neupert W, Langer T. Chaperone-like activity of the AAA domain of the yeast Yme1 AAA protease. Nature. 1999 Mar 25;398(6725):348–351. [PubMed]
  • Klanner C, Prokisch H, Langer T. MAP-1 and IAP-1, two novel AAA proteases with catalytic sites on opposite membrane surfaces in mitochondrial inner membrane of Neurospora crassa. Mol Biol Cell. 2001 Sep;12(9):2858–2869. [PMC free article] [PubMed]
  • Fonknechten N, Mavel D, Byrne P, Davoine CS, Cruaud C, Bönsch D, Boentsch D, Samson D, Coutinho P, Hutchinson M, et al. Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. Hum Mol Genet. 2000 Mar 1;9(4):637–644. [PubMed]
  • Meijer Inge A, Hand Collette K, Cossette P, Figlewicz Denise A, Rouleau Guy A. Spectrum of SPG4 mutations in a large collection of North American families with hereditary spastic paraplegia. Arch Neurol. 2002 Feb;59(2):281–286. [PubMed]
  • Sauter S, Miterski B, Klimpe S, Bönsch D, Schöls L, Visbeck A, Papke T, Hopf HC, Engel W, Deufel T, et al. Mutation analysis of the spastin gene (SPG4) in patients in Germany with autosomal dominant hereditary spastic paraplegia. Hum Mutat. 2002 Aug;20(2):127–132. [PubMed]
  • Bürger J, Fonknechten N, Hoeltzenbein M, Neumann L, Bratanoff E, Hazan J, Reis A. Hereditary spastic paraplegia caused by mutations in the SPG4 gene. Eur J Hum Genet. 2000 Oct;8(10):771–776. [PubMed]
  • Hentati A, Deng HX, Zhai H, Chen W, Yang Y, Hung WY, Azim AC, Bohlega S, Tandan R, Warner C, et al. Novel mutations in spastin gene and absence of correlation with age at onset of symptoms. Neurology. 2000 Nov 14;55(9):1388–1390. [PubMed]
  • Svenson IK, Ashley-Koch AE, Gaskell PC, Riney TJ, Cumming WJ, Kingston HM, Hogan EL, Boustany RM, Vance JM, Nance MA, et al. Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia. Am J Hum Genet. 2001 May;68(5):1077–1085. [PMC free article] [PubMed]
  • Lindsey JC, Lusher ME, McDermott CJ, White KD, Reid E, Rubinsztein DC, Bashir R, Hazan J, Shaw PJ, Bushby KM. Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis. J Med Genet. 2000 Oct;37(10):759–765. [PMC free article] [PubMed]
  • Proukakis Christos, Hart Paul E, Cornish Amy, Warner Thomas T, Crosby Andrew H. Three novel spastin (SPG4) mutations in families with autosomal dominant hereditary spastic paraplegia. J Neurol Sci. 2002 Sep 15;201(1-2):65–69. [PubMed]
  • Errico Alessia, Ballabio Andrea, Rugarli Elena I. Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics. Hum Mol Genet. 2002 Jan 15;11(2):153–163. [PubMed]
  • Goldstein LS. Kinesin molecular motors: transport pathways, receptors, and human disease. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):6999–7003. [PMC free article] [PubMed]
  • Miki H, Setou M, Kaneshiro K, Hirokawa N. All kinesin superfamily protein, KIF, genes in mouse and human. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7004–7011. [PMC free article] [PubMed]
  • Kanai Y, Okada Y, Tanaka Y, Harada A, Terada S, Hirokawa N. KIF5C, a novel neuronal kinesin enriched in motor neurons. J Neurosci. 2000 Sep 1;20(17):6374–6384. [PubMed]
  • Song H, Endow SA. Decoupling of nucleotide- and microtubule-binding sites in a kinesin mutant. Nature. 1998 Dec 10;396(6711):587–590. [PubMed]
  • Zhao C, Takita J, Tanaka Y, Setou M, Nakagawa T, Takeda S, Yang HW, Terada S, Nakata T, Takei Y, et al. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell. 2001 Jun 1;105(5):587–597. [PubMed]
  • Tanaka Y, Kanai Y, Okada Y, Nonaka S, Takeda S, Harada A, Hirokawa N. Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria. Cell. 1998 Jun 26;93(7):1147–1158. [PubMed]
  • Muglia Maria, Magariello Angela, Nicoletti Giuseppe, Patitucci Alessandra, Gabriele Anna Lia, Conforti Francesca Luisa, Mazzei Rosalucia, Caracciolo Manuela, Ardito Bonaventura, Lastilla Marcello, et al. Further evidence that SPG3A gene mutations cause autosomal dominant hereditary spastic paraplegia. Ann Neurol. 2002 Jun;51(6):794–795. [PubMed]

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