hereditary spastic paraplegia

Summary

Summary: A group of inherited diseases that share similar phenotypes but are genetically diverse. Different genetic loci for autosomal recessive, autosomal dominant, and x-linked forms of hereditary spastic paraplegia have been identified. Clinically, patients present with slowly progressive distal limb weakness and lower extremity spasticity. Peripheral sensory neurons may be affected in the later stages of the disease. (J Neurol Neurosurg Psychiatry 1998 Jan;64(1):61-6; Curr Opin Neurol 1997 Aug;10(4):313-8)

Top Publications

  1. Iwanaga H, Tsujino A, Shirabe S, Eguchi H, Fukushima N, Niikawa N, et al. Large deletion involving the 5'-UTR in the spastin gene caused mild phenotype of autosomal dominant hereditary spastic paraplegia. Am J Med Genet A. 2005;133A:13-7 pubmed
    b>Hereditary spastic paraplegia (HSP) due to mutations in the spastin gene (SPG4) located to 2p22-p21 is the most common form of autosomal dominant (AD) HSP...
  2. Wang X, Shaw W, Tsang H, Reid E, O Kane C. Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules. Nat Neurosci. 2007;10:177-85 pubmed
    To understand the functions of NIPA1, mutated in the neurodegenerative disease hereditary spastic paraplegia, and of ichthyin, mutated in autosomal recessive congenital ichthyosis, we have studied their Drosophila melanogaster ortholog, ..
  3. Lossos A, Stevanin G, Meiner V, Argov Z, Bouslam N, Newman J, et al. Hereditary spastic paraplegia with thin corpus callosum: reduction of the SPG11 interval and evidence for further genetic heterogeneity. Arch Neurol. 2006;63:756-60 pubmed
    b>Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) is an autosomal recessive form of complicated HSP mainly characterized by slowly progressive spastic paraparesis and mental deterioration beginning in the second decade ..
  4. Okubo S, Ueda M, Kamiya T, Mizumura S, Terashi A, Katayama Y. Neurological and neuroradiological progression in hereditary spastic paraplegia with a thin corpus callosum. Acta Neurol Scand. 2000;102:196-9 pubmed
    We followed-up a Japanese man suffering from hereditary spastic paraplegia with a thin corpus callosum (HSP-TCC) by single photon emission computed tomography (SPECT) using 123IN-isopropyl-piodoamphetamine (123I-IMP) over 4 years (25 to ..
  5. Liao S, Shen L, Du J, Zhao G, Wang X, Yang Y, et al. Novel mutations of the SPG11 gene in hereditary spastic paraplegia with thin corpus callosum. J Neurol Sci. 2008;275:92-9 pubmed publisher
    b>Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a clinically and genetically heterogeneous neurodegenerative disorder with genetic linkage to multi-loci...
  6. Warnecke T, Duning T, Schwan A, Lohmann H, Epplen J, Young P. A novel form of autosomal recessive hereditary spastic paraplegia caused by a new SPG7 mutation. Neurology. 2007;69:368-75 pubmed
    b>Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by progressive spastic paraparesis of the lower limbs.
  7. Wilkinson P, Hart P, Patel H, Warner T, Crosby A. SPG3A mutation screening in English families with early onset autosomal dominant hereditary spastic paraplegia. J Neurol Sci. 2003;216:43-5 pubmed
    ..gene encoding the novel GTPase atlastin have recently been implicated in causing autosomal dominant hereditary spastic paraplegia (ADHSP) in six unrelated families...
  8. Murphy S, Gorman G, Beetz C, Byrne P, Dytko M, McMonagle P, et al. Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence. Neurology. 2009;73:378-84 pubmed publisher
    ..There has only been one postmortem examination described; not all accept that progressive cognitive decline is a feature of this disorder...
  9. Shoukier M, Neesen J, Sauter S, Argyriou L, Doerwald N, Pantakani D, et al. Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia. Eur J Hum Genet. 2009;17:187-94 pubmed publisher
    ..encoding for spastin plays a central role in the genetically heterogeneous group of diseases termed hereditary spastic paraplegia (HSP)...

More Information

Publications62

  1. Martinelli P, La Mattina V, Bernacchia A, Magnoni R, Cerri F, Cox G, et al. Genetic interaction between the m-AAA protease isoenzymes reveals novel roles in cerebellar degeneration. Hum Mol Genet. 2009;18:2001-13 pubmed publisher
    ..Loss of function of paraplegin (encoded by the SPG7 gene) causes hereditary spastic paraplegia, a disease characterized by retrograde degeneration of cortical motor axons...
  2. Braschinsky M, Zopp I, Kals M, Haldre S, Gross Paju K. Bladder dysfunction in hereditary spastic paraplegia: what to expect?. J Neurol Neurosurg Psychiatry. 2010;81:263-6 pubmed publisher
    b>Hereditary spastic paraplegia (HSP) comprises a group of rare neurodegenerative disorders characterised by progressive spasticity and hyperreflexia of the legs...
  3. Simpson M, Cross H, Proukakis C, Pryde A, Hershberger R, Chatonnet A, et al. Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia. Am J Hum Genet. 2003;73:1147-56 pubmed
    Mast syndrome is an autosomal recessive, complicated form of hereditary spastic paraplegia with dementia that is present at high frequency among the Old Order Amish...
  4. Proukakis C, Auer Grumbach M, Wagner K, Wilkinson P, Reid E, Patton M, et al. Screening of patients with hereditary spastic paraplegia reveals seven novel mutations in the SPG4 (Spastin) gene. Hum Mutat. 2003;21:170 pubmed
    b>Hereditary spastic paraplegia (HSP) is a heterogeneous condition characterised in its pure form by progressive lower limb spasticity. Mutations in SPG4 (encoding spastin) may be responsible for up to 40% of autosomal dominant (AD) cases...
  5. Hooper C, Puttamadappa S, Loring Z, Shekhtman A, Bakowska J. Spartin activates atrophin-1-interacting protein 4 (AIP4) E3 ubiquitin ligase and promotes ubiquitination of adipophilin on lipid droplets. BMC Biol. 2010;8:72 pubmed publisher
    ..receptor and turnover of lipid droplets and a lack of expression of this protein is responsible for hereditary spastic paraplegia type 20 (SPG20)...
  6. Tallaksen C, Durr A, Brice A. Recent advances in hereditary spastic paraplegia. Curr Opin Neurol. 2001;14:457-63 pubmed
    ..Surprisingly, the five genes encode proteins of different families, making understanding and diagnosis of HSP even more difficult. The discovery of new genes should hopefully help to clarify the pathophysiology of these disorders...
  7. Ivanova N, Claeys K, Deconinck T, Litvinenko I, Jordanova A, Auer Grumbach M, et al. Hereditary spastic paraplegia 3A associated with axonal neuropathy. Arch Neurol. 2007;64:706-13 pubmed
    To study the frequency and distribution of mutations in SPG3A in a large cohort of patients with hereditary spastic paraplegia.
  8. Hansen J, Durr A, Cournu Rebeix I, Georgopoulos C, Ang D, Nielsen M, et al. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am J Hum Genet. 2002;70:1328-32 pubmed
    SPG13, an autosomal dominant form of pure hereditary spastic paraplegia, was recently mapped to chromosome 2q24-34 in a French family...
  9. Roll Mecak A, Vale R. Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin. Nature. 2008;451:363-7 pubmed publisher
    ..Our work also provides insights into the structural defects in spastin that arise from mutations identified in hereditary spastic paraplegia patients.
  10. Errico A, Ballabio A, Rugarli E. Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics. Hum Mol Genet. 2002;11:153-63 pubmed
    b>Hereditary spastic paraplegia (HSP) is characterized by progressive weakness and spasticity of the lower limbs, caused by the specific degeneration of the corticospinal tracts, the longest axons in humans...
  11. Hourani R, El Hajj T, Barada W, Hourani M, Yamout B. MR imaging findings in autosomal recessive hereditary spastic paraplegia. AJNR Am J Neuroradiol. 2009;30:936-40 pubmed publisher
    b>Hereditary spastic paraplegia (HSP) is a disorder characterized by degeneration of the corticospinal tracts and posterior column of the spinal cord...
  12. Bakowska J, Wang H, Xin B, Sumner C, Blackstone C. Lack of spartin protein in Troyer syndrome: a loss-of-function disease mechanism?. Arch Neurol. 2008;65:520-4 pubmed publisher
    ..This mutation is predicted to cause premature termination of the spartin protein. However, it remains unknown whether this truncated spartin protein is absent or is present and partially functional in patients...
  13. Depienne C, Stevanin G, Brice A, Durr A. Hereditary spastic paraplegias: an update. Curr Opin Neurol. 2007;20:674-80 pubmed
    ..Cerebral MRI and the familial history of each patient with spastic paraplegia are the minimal clinical elements needed to orient genetic testing...
  14. Hansen J, Svenstrup K, Ang D, Nielsen M, Christensen J, Gregersen N, et al. A novel mutation in the HSPD1 gene in a patient with hereditary spastic paraplegia. J Neurol. 2007;254:897-900 pubmed
    ..In the present work we have investigated 23 Danish index patients with hereditary spastic paraplegia (HSP) for mutations in the HSPD1 gene. One patient was found to be heterozygous for a c...
  15. Hecht M, Stolze H, Auf dem Brinke M, Giess R, Treig T, Winterholler M, et al. Botulinum neurotoxin type A injections reduce spasticity in mild to moderate hereditary spastic paraplegia--report of 19 cases. Mov Disord. 2008;23:228-33 pubmed
    b>Hereditary spastic paraplegia (HSP) is characterized by lower extremity spasticity. Symptomatic therapy generally includes physical therapy and oral antispastic agents, in selected cases intrathecal baclofen...
  16. Kuru S, Sakai M, Konagaya M, Yoshida M, Hashizume Y. Autopsy case of hereditary spastic paraplegia with thin corpus callosum showing severe gliosis in the cerebral white matter. Neuropathology. 2005;25:346-52 pubmed
    We report an autopsy case of a 51-year-old man clinically diagnosed with a complicated type of hereditary spastic paraplegia. His sister showed similar manifestations. Gait disturbance was manifested at 14 years of age...
  17. Strong M, Gordon P. Primary lateral sclerosis, hereditary spastic paraplegia and amyotrophic lateral sclerosis: discrete entities or spectrum?. Amyotroph Lateral Scler Other Motor Neuron Disord. 2005;6:8-16 pubmed
    ..Only through the development and application of exacting clinical diagnostic criteria to epidemiological studies, along with greater numbers of post-mortem examinations, however, will these questions be answered fully...
  18. Soderblom C, Blackstone C. Traffic accidents: molecular genetic insights into the pathogenesis of the hereditary spastic paraplegias. Pharmacol Ther. 2006;109:42-56 pubmed
    ..Through a better understanding of the functions of the HSP gene products, novel therapeutic targets for treatment and prevention are being identified...
  19. Orthmann Murphy J, Salsano E, Abrams C, Bizzi A, Uziel G, Freidin M, et al. Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. Brain. 2009;132:426-38 pubmed publisher
    ..Thus, GJA12/GJC2 mutations can result in a milder phenotype than previously appreciated, but whether I33M retains a function of Cx47 not directly related to forming functional gap junction channels is not known...
  20. Reid E, Connell J, Edwards T, Duley S, Brown S, Sanderson C. The hereditary spastic paraplegia protein spastin interacts with the ESCRT-III complex-associated endosomal protein CHMP1B. Hum Mol Genet. 2005;14:19-38 pubmed
    Pure hereditary spastic paraplegia is characterized by length-dependent degeneration of the distal ends of long axons. Mutations in spastin are the most common cause of the condition...
  21. Stevanin G, Santorelli F, Azzedine H, Coutinho P, Chomilier J, Denora P, et al. Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet. 2007;39:366-72 pubmed
    Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected ..
  22. Somasundaram S, Raghavendra S, Singh A, Kesavadas C, Nair M. Hereditary spastic paraplegia with a thin corpus callosum. Pediatr Radiol. 2007;37:503-5 pubmed
    We report a 15-year-old boy with autosomal recessive complicated hereditary spastic paraplegia with a thin corpus callosum (HSP-TCC)...
  23. Schlang K, Arning L, Epplen J, Stemmler S. Autosomal dominant hereditary spastic paraplegia: novel mutations in the REEP1 gene (SPG31). BMC Med Genet. 2008;9:71 pubmed publisher
    ..and in the SPG3A gene (atlastin) account for the majority of 'pure' autosomal dominant form of hereditary spastic paraplegia (HSP)...
  24. Braschinsky M, Parts K, Maamägi H, Gross Paju K, Haldre S. Functional assessment of lower extremities in hereditary spastic paraplegia. Arch Phys Med Rehabil. 2009;90:1887-90 pubmed publisher
    To characterize the spasticity and range of motion (ROM) in patients with hereditary spastic paraplegia (HSP) and to correlate these parameters with walking speed.
  25. Rainier S, Chai J, Tokarz D, Nicholls R, Fink J. NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6). Am J Hum Genet. 2003;73:967-71 pubmed
    ..Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications...
  26. Du F, Ozdowski E, Kotowski I, Marchuk D, Sherwood N. Functional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia. Hum Mol Genet. 2010;19:1883-96 pubmed publisher
    Mutations in spastin are the most frequent cause of the neurodegenerative disease autosomal dominant-hereditary spastic paraplegia (AD-HSP)...
  27. Burger J, Fonknechten N, Hoeltzenbein M, Neumann L, Bratanoff E, Hazan J, et al. Hereditary spastic paraplegia caused by mutations in the SPG4 gene. Eur J Hum Genet. 2000;8:771-6 pubmed
    Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a genetically heterogeneous neurodegenerative disorder characterised by progressive spasticity of the lower limbs...
  28. Erichsen A, Inderhaug E, Mattingsdal M, Eiklid K, Tallaksen C. Seven novel mutations and four exon deletions in a collection of Norwegian patients with SPG4 hereditary spastic paraplegia. Eur J Neurol. 2007;14:809-14 pubmed
    ..the phenotypic variation and frequency of SPAST mutations or deletions in Norwegian patients with hereditary spastic paraplegia (HSP), we examined 59 unrelated patients with HSP and screened for DNA point mutations and ..
  29. de Bot S, van den Elzen R, Mensenkamp A, Schelhaas H, Willemsen M, Knoers N, et al. Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations. J Neurol Neurosurg Psychiatry. 2010;81:1073-8 pubmed publisher
    ..In the clinically and genetically heterogeneous group of the hereditary spastic paraplegias (HSPs), mutations in the SPAST gene are most frequently found and cause a pure autosomal dominant form...
  30. McMonagle P, Webb S, Hutchinson M. The prevalence of "pure" autosomal dominant hereditary spastic paraparesis in the island of Ireland. J Neurol Neurosurg Psychiatry. 2002;72:43-6 pubmed
    ..Previous studies have included autosomal recessive and sporadic cases in prevalence calculations. This study aimed to determine the prevalence and features of pure ADHSP in the island of Ireland...
  31. Depienne C, Fedirko E, Forlani S, Cazeneuve C, Ribai P, Feki I, et al. Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia. J Med Genet. 2007;44:281-4 pubmed
    Point mutations in SPG4, the gene encoding spastin, are a frequent cause of autosomal dominant hereditary spastic paraplegia (AD-HSP). However, standard methods for genetic analyses fail to detect exonic microdeletions.
  32. Blair M, Ma S, Hedera P. Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia. Neurogenetics. 2006;7:47-50 pubmed
    Autosomal dominant hereditary spastic paraplegia (AD HSP) linked to chromosome 12q (SPG10) is caused by mutations in the neuronal kinesin heavy-chain KIF5A gene...
  33. Jørgensen L, Nielsen J, Ravnborg M. MEP recruitment curves in multiple sclerosis and hereditary spastic paraplegia. J Neurol Sci. 2005;237:25-9 pubmed
    ..Multiple sclerosis (MS) represents both demyelination and axonal degeneration. Hereditary Spastic Paraplegia (HSP) was included as a model of pure axonal loss.
  34. Valdmanis P, Meijer I, Reynolds A, Lei A, Macleod P, Schlesinger D, et al. Mutations in the KIAA0196 gene at the SPG8 locus cause hereditary spastic paraplegia. Am J Hum Genet. 2007;80:152-61 pubmed
    b>Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. The eighth HSP locus, SPG8, is on chromosome 8p24.13...
  35. Fichera M, Lo Giudice M, Falco M, Sturnio M, Amata S, Calabrese O, et al. Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary spastic paraplegia. Neurology. 2004;63:1108-10 pubmed
    ..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...
  36. Seidel K, De Vos R, Derksen L, Bauer P, Riess O, den Dunnen W, et al. Widespread thalamic and cerebellar degeneration in a patient with a complicated hereditary spastic paraplegia (HSP). Ann Anat. 2009;191:203-11 pubmed publisher
    ..In view of their known functional role, damage to these central nervous gray and white matter components offers explanations for the patient's pyramidal signs, her cerebellar, psychiatric and neuropsychological disease symptoms...
  37. Albin R, Koeppe R, Rainier S, Fink J. Normal dopaminergic nigrostriatal innervation in SPG3A hereditary spastic paraplegia. J Neurogenet. 2008;22:289-94 pubmed publisher
    SPG3A/atlastin-1 gene mutations cause an autosomal dominant form of hereditary spastic paraplegia (SPG3A-HSP)...
  38. Roll Mecak A, Vale R. The Drosophila homologue of the hereditary spastic paraplegia protein, spastin, severs and disassembles microtubules. Curr Biol. 2005;15:650-5 pubmed
    ..We show that D-spastin, like katanin, displays ATPase activity and uses energy from ATP hydrolysis to sever and disassemble microtubules; disease mutations abolish or partially interfere with these activities...
  39. Rowland L. Primary lateral sclerosis, hereditary spastic paraplegia, and mutations in the alsin gene: historical background for the first International Conference. Amyotroph Lateral Scler Other Motor Neuron Disord. 2005;6:67-76 pubmed
  40. Thomas I, Thomas M, Scrutton M. Spinal anaesthesia in a patient with hereditary spastic paraplegia: case report and literature review. Int J Obstet Anesth. 2006;15:254-6 pubmed
    We report the use of spinal anaesthesia in a patient with hereditary spastic paraplegia who presented for manual removal of placenta following a normal vaginal delivery...
  41. Orso G, Martinuzzi A, Rossetto M, Sartori E, Feany M, Daga A. Disease-related phenotypes in a Drosophila model of hereditary spastic paraplegia are ameliorated by treatment with vinblastine. J Clin Invest. 2005;115:3026-34 pubmed
  42. Milano A, Montesano Gesualdi N, Teperino R, Esposito F, Cocozza S, Ungaro P. Oxidative DNA damage and activation of c-Jun N-terminal kinase pathway in fibroblasts from patients with hereditary spastic paraplegia. Cell Mol Neurobiol. 2005;25:1245-54 pubmed
    1. Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative disorders affecting 1 in 10,000 individuals...
  43. DeLuca G, Ebers G, Esiri M. The extent of axonal loss in the long tracts in hereditary spastic paraplegia. Neuropathol Appl Neurobiol. 2004;30:576-84 pubmed
    b>Hereditary spastic paraplegia (HSP) comprises a group of inherited neurodegenerative disorders with the shared characteristics of progressive weakness and spasticity predominantly affecting the lower limbs...
  44. Eastman S, Yassaee M, Bieniasz P. A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover. J Cell Biol. 2009;184:881-94 pubmed publisher
    ..These experiments suggest functions for ubiquitin ligases and SPG20 in the regulation of LD turnover and potential pathological mechanisms in Troyer syndrome...
  45. Edgar J, McLaughlin M, Yool D, Zhang S, Fowler J, Montague P, et al. Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia. J Cell Biol. 2004;166:121-31 pubmed
    ..Using a mouse model of hereditary spastic paraplegia type 2 due to a null mutation of the myelin Plp gene, we find a progressive impairment in fast ..
  46. Robay D, Patel H, Simpson M, Brown N, Crosby A. Endogenous spartin, mutated in hereditary spastic paraplegia, has a complex subcellular localization suggesting diverse roles in neurons. Exp Cell Res. 2006;312:2764-77 pubmed
    Mutation of spartin (SPG20) underlies a complicated form of hereditary spastic paraplegia, a disorder principally defined by the degeneration of upper motor neurons...
  47. Mannan A, Krawen P, Sauter S, Boehm J, Chronowska A, Paulus W, et al. ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary spastic paraplegia. Am J Hum Genet. 2006;79:351-7 pubmed
    Spastin, the most commonly mutated protein in the autosomal dominant form of hereditary spastic paraplegia (AD-HSP) has been suggested to be involved in vesicular cargo trafficking; however, a comprehensive function of spastin has not ..
  48. Klebe S, Stolze H, Kopper F, Lorenz D, Wenzelburger R, Volkmann J, et al. Gait analysis of sporadic and hereditary spastic paraplegia. J Neurol. 2004;251:571-8 pubmed
    ..Spastic paraparesis is the major and most disabling clinical symptom and was assessed with gait analysis using a three-dimensional infrared movement analysis system...
  49. Yip A, Durr A, Marchuk D, Ashley Koch A, Hentati A, Rubinsztein D, et al. Meta-analysis of age at onset in spastin-associated hereditary spastic paraplegia provides no evidence for a correlation with mutational class. J Med Genet. 2003;40:e106 pubmed
  50. Park S, Zhu P, Parker R, Blackstone C. Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network. J Clin Invest. 2010;120:1097-110 pubmed publisher
    ..Thus, defects in tubular ER shaping and network interactions with the microtubule cytoskeleton seem to be the predominant pathogenic mechanism of HSP...
  51. Teive H, Iwamoto F, Camargo C, Lopes Cendes I, Werneck L. Machado-Joseph disease versus hereditary spastic paraplegia: case report. Arq Neuropsiquiatr. 2001;59:809-11 pubmed
    ..We report the case of 41-year-old woman with the phenotype of complicated hereditary spastic paraplegia. Her father died at the age of 56 years due to an undiagnosed progressive neurological disease that ..
  52. Tzoulis C, Denora P, Santorelli F, Bindoff L. Hereditary spastic paraplegia caused by the novel mutation 1047insC in the SPG7 gene. J Neurol. 2008;255:1142-4 pubmed publisher
    ..1047insC, in a non-consanguineous Norwegian family with ARHSP. This is the first description of this disorder in the Norwegian population and, apart from mild ptosis in two siblings, the phenotype was essentially pure and late in onset...
  53. Al Yahyaee S, al Gazali L, De Jonghe P, Al Barwany H, Al Kindi M, De Vriendt E, et al. A novel locus for hereditary spastic paraplegia with thin corpus callosum and epilepsy. Neurology. 2006;66:1230-4 pubmed
    b>Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity occurs in isolation or complicated when other neurologic abnormalities are present...