title: SPG3A mutation screening in English families with early onset autosomal dominant hereditary spastic paraplegia.
abstract: Mutations in the SPG3A gene encoding the novel GTPase atlastin have recently been implicated in causing autosomal dominant hereditary spastic paraplegia (ADHSP) in six unrelated families. The phenotype of affected individuals in all cases has been of an early onset uncomplicated form of the disease. One particular missense mutation, R239C, in exon 7 of SPG3A has been identified in three of these families. We performed mutation screening by direct sequencing of all 14 exons and flanking sequences of the SPG3A gene in affected individuals from 12 unrelated English families, all with an early onset uncomplicated ADHSP in whom spastin mutations had previously been excluded. The R239C mutation was found to co-segregate with the disease in one English ADHSP family confirming a widespread prevalence for this commonly occurring mutation. No additional SPG3A mutations were identified in the remaining 11 families suggesting that even within this specific sub-set of early onset uncomplicated ADHSP patients atlastin mutations are relatively rare.
authors: Department of Medical Genetics, St. George's Hospital Medical School, Cranmer Terrace Tooting, London, SW17 0RE, UK.
authors: P A
authors: PA
authors: Wilkinson
authors: P E
authors: PE
authors: Hart
authors: H
authors: H
authors: Patel
authors: T T
authors: TT
authors: Warner
authors: A H
authors: AH
authors: Crosby
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004739:England; D005091:Exons / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D019204:GTP-Binding Proteins; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C440006:ATL1 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins