title: Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia.
abstract: The hereditary spastic paraplegias (HSPs; Strümpell-Lorrain syndrome, MIM number 18260) are a diverse class of disorders characterized by insidiously progressive lower-extremity spastic weakness (reviewed in refs. 1-3). Eight autosomal dominant HSP (ADHSP) loci have been identified, the most frequent of which is that linked to the SPG4 locus on chromosome 2p22 (found in approximately 42%), followed by that linked to the SPG3A locus on chromosome 14q11-q21 (in approximately 9%). Only SPG4 has been identified as a causative gene in ADHSP. Its protein (spastin) is predicted to participate in the assembly or function of nuclear protein complexes. Here we report the identification of mutations in a newly identified GTPase gene, SPG3A, in ADHSP affected individuals.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: D
authors.initials: D
authors.lastname: Alvarado
authors.forename: S
authors.initials: S
authors.lastname: Rainier
authors.forename: R
authors.initials: R
authors.lastname: Lemons
authors.forename: P
authors.initials: P
authors.lastname: Hedera
authors.forename: C H
authors.initials: CH
authors.lastname: Weber
authors.forename: T
authors.initials: T
authors.lastname: Tukel
authors.forename: M
authors.initials: M
authors.lastname: Apak
authors.forename: T
authors.initials: T
authors.lastname: Heiman-Patterson
authors.forename: L
authors.initials: L
authors.lastname: Ming
authors.forename: M
authors.initials: M
authors.lastname: Bui
authors.forename: J K
authors.initials: JK
authors.lastname: Fink
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003001:Cloning, Molecular; D020451:Contig Mapping; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D019204:GTP-Binding Proteins; D006801:Humans; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; C440006:ATL1 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins