title: Novel mutations in the Atlastin gene (SPG3A) in families with autosomal dominant hereditary spastic paraplegia and evidence for late onset forms of HSP linked to the SPG3A locus.
abstract: Hereditary spastic paraplegias (HSP) comprise a genetically and clinically heterogeneous group of neurodegenerative disorders characterised by progressive spasticity and hyperreflexia of the lower limbs. Autosomal dominant hereditary spastic paraplegia linked to the SPG3A locus on chromosome 14q11-21 accounts for approximately 10% of autosomal dominant hereditary spastic paraplegia (ADHSP). It is caused by mutations in the SPG3A gene encoding the protein atlastin. To date, only five disease-causing mutations in the SPG3A gene have been described. We analysed 13 SPG4-negative families for mutations in the SPG3A gene and identified a mutation in 38% (5/13). Two of the mutations are novel, c.481G>C (p.A161P) and c.740A>C (p.H247P). One of the novel mutations was found both in a family with early onset of symptoms and in a late onset family. Furthermore, we report on numerous polymorphisms detected in the SPG3A gene.
authors.affiliation: Institute of Human Genetics, University of Göttingen, Germany. ssauter@gwdg.de
authors.forename: S M
authors.initials: SM
authors.lastname: Sauter
authors.forename: W
authors.initials: W
authors.lastname: Engel
authors.forename: L M
authors.initials: LM
authors.lastname: Neumann
authors.forename: J
authors.initials: J
authors.lastname: Kunze
authors.forename: J
authors.initials: J
authors.lastname: Neesen
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D019204:GTP-Binding Proteins; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C440006:ATL1 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins