Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia

Nat Genet. 2001 Nov;29(3):326-31. doi: 10.1038/ng758.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Chromosomes, Human, Pair 2 / genetics
  • Cloning, Molecular
  • Contig Mapping
  • Female
  • GTP Phosphohydrolases / genetics*
  • GTP-Binding Proteins
  • Humans
  • Lod Score
  • Male
  • Membrane Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Protein Conformation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Spastic Paraplegia, Hereditary / genetics*

Substances

  • Membrane Proteins
  • RNA, Messenger
  • ATL1 protein, human
  • GTP Phosphohydrolases
  • GTP-Binding Proteins

Associated data

  • GENBANK/AF131801
  • GENBANK/AY032844
  • OMIM/18260
  • RefSeq/NM_015915
  • RefSeq/NT_010035