ONLINE MUTATION REPORT

Meta-analysis of age at onset in spastin-associated hereditary spastic paraplegia provides no evidence for a correlation with mutational class

A G Yip¹, A Dürr², D A Marchuk³, A Ashley-Koch⁴, A Hentati⁵, D C Rubinsztein⁶, E Reid⁶

¹ Genetics Program (Department of Medicine), Boston University School of Medicine, Boston, MA 02118, USA
² INSERM U 289 and Département de Génétique, Cytogénétique et Embryologie, Hôpital de la Salpêtrière, Paris, France
³ Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
⁴ Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA
⁵ Department of Neurology, Northwestern University Medical School Chicago, 300 E. Superior Street, Tarry 13-715, Chicago, IL 60611, USA
⁶ Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, University of Cambridge, Cambridge, UK

Correspondence to:
Correspondence to:
Dr E Reid, Department of Medical Genetics, University of Cambridge, Box 134, Addenbrooke’s Hospital, Cambridge CB2 2QQ UK;
ereid@hgmp.mrc.ac.uk

Abbreviations: HSP, hereditary spastic paraplegia

Keywords: hereditary spastic paraplegia; spastin

The first 150 words of the full text of this article appear below.

The hereditary spastic paraplegias (HSPs) are a group of single gene disorders in which the corticospinal tracts fail to develop normally, or degenerate after initially normal development. The HSPs all share the principal clinical feature of progressive lower limb spastic paralysis, and are subdivided into pure and complicated forms, depending on the presence of additional neurological or non-neurological features.^1,2

The pure HSPs tend to be associated with neurodegeneration, rather than abnormal development, and histopathological studies in pure HSP show a length-dependent "dying back" of the terminal ends of the corticospinal tract axons, with the longest axons being involved first.¹ The SPG4 gene, spastin, is the most important pure HSP gene, being responsible for approximately 40% of definite autosomal dominant pure HSP and a smaller proportion of sporadic cases and cases with uncertain family history.^3,4 The 616 amino acid spastin protein is a widely expressed AAA (ATPases associated with diverse cellular . . . [Full text of this article]

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