title: Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60.
abstract: SPG13, an autosomal dominant form of pure hereditary spastic paraplegia, was recently mapped to chromosome 2q24-34 in a French family. Here we present genetic data indicating that SPG13 is associated with a mutation, in the gene encoding the human mitochondrial chaperonin Hsp60, that results in the V72I substitution. A complementation assay showed that wild-type HSP60 (also known as "HSPD1"), but not HSP60 (V72I), together with the co-chaperonin HSP10 (also known as "HSPE1"), can support growth of Escherichia coli cells in which the homologous chromosomal groESgroEL chaperonin genes have been deleted. Taken together, our data strongly indicate that the V72I variation is the first disease-causing mutation that has been identified in HSP60.
authors.affiliation: Research Unit for Molecular Medicine, Arhus University Hospital and Faculty of Health Sciences, Arhus, Denmark.
authors.forename: Jens Jacob
authors.initials: JJ
authors.lastname: Hansen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cournu-Rebeix
authors.forename: Costa
authors.initials: C
authors.lastname: Georgopoulos
authors.forename: Debbie
authors.initials: D
authors.lastname: Ang
authors.forename: Marit Nyholm
authors.initials: MN
authors.lastname: Nielsen
authors.forename: Claire-Sophie
authors.initials: CS
authors.lastname: Davoine
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Bertrand
authors.initials: B
authors.lastname: Fontaine
authors.forename: Niels
authors.initials: N
authors.lastname: Gregersen
authors.forename: Peter
authors.initials: P
authors.lastname: Bross
mesh_terms: D000483:Alleles; D015153:Blotting, Western; D018835:Chaperonin 10 / Q000235:genetics / Q000378:metabolism; D018834:Chaperonin 60 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005816:Genetic Complementation Test; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009876:Operon / Q000235:genetics; D010375:Pedigree; D011487:Protein Conformation; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D018835:Chaperonin 10; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D024101:Mitochondrial Proteins