title: Characterization of a novel SPG3A deletion in a French-Canadian family.
abstract: Hereditary spastic paraplegias (HSPs) are characterized by progressive lower limb spasticity and weakness. Mutations in the SPG3A gene, which encodes the large guanosine triphosphatase atlastin, are the second most common cause of autosomal dominant hereditary spastic paraplegia. In a large SPG3A screen of 70 hereditary spastic paraplegia subjects, a novel in-frame deletion, p.del436N, was identified. Characterization of this deletion showed that it affects neither the guanosine triphosphatase activity of atlastin nor interactions between atlastin and spastin. Interestingly, immunoblot analysis of lymphoblasts from affected patients demonstrated a significant reduction in atlastin protein levels, supporting a loss-of-function disease mechanism.
authors.affiliation: Center for the Study of Brain Diseases, Centre Hospitalier de l'Université de Montréal Research Center-Notre-Dame Hospital, University of Montreal, Québec, Canada.
authors.forename: Inge A
authors.initials: IA
authors.lastname: Meijer
authors.forename: Patrick
authors.initials: P
authors.lastname: Dion
authors.forename: Sandra
authors.initials: S
authors.lastname: Laurent
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupré
authors.forename: Bernard
authors.initials: B
authors.lastname: Brais
authors.forename: Annie
authors.initials: A
authors.lastname: Levert
authors.forename: Jacques
authors.initials: J
authors.lastname: Puymirat
authors.forename: Marie France
authors.initials: MF
authors.lastname: Rioux
authors.forename: Michel
authors.initials: M
authors.lastname: Sylvain
authors.forename: Peng-Peng
authors.initials: PP
authors.lastname: Zhu
authors.forename: Cynthia
authors.initials: C
authors.lastname: Soderblom
authors.forename: Julia
authors.initials: J
authors.lastname: Stadler
authors.forename: Craig
authors.initials: C
authors.lastname: Blackstone
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004568:Electrodiagnosis; D005190:Family; D020558:GTP Phosphohydrolases / Q000032:analysis / Q000235:genetics*; D019204:GTP-Binding Proteins; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008565:Membrane Proteins; D008875:Middle Aged; D010264:Paraplegia / Q000175:diagnosis / Q000235:genetics*; D011792:Quebec; D012333:RNA, Messenger / Q000032:analysis; D017384:Sequence Deletion / Q000235:genetics*; D020798:Two-Hybrid System Techniques
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; C440006:ATL1 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins