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.
MeSH Terms
Alleles
Blotting, Western
Chaperonin 10/genetics,metabolism
Chaperonin 60/chemistry,genetics,metabolism
Chromosome Mapping
Escherichia coli/genetics
Escherichia coli Proteins/genetics,metabolism
Female
Genetic Complementation Test
Humans
Male
Mitochondrial Proteins/genetics,metabolism
Models, Molecular
Molecular Sequence Data
Mutation/genetics
Operon/genetics
Pedigree
Protein Conformation
Spastic Paraplegia, Hereditary/genetics
Chemicals
Chaperonin 10
Chaperonin 60
Escherichia coli Proteins
Mitochondrial Proteins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Hansen Jens Jacob
Research Unit for Molecular Medicine, Arhus University Hospital and Faculty of Health Sciences, Arhus, Denmark.
Dürr Alexandra
Cournu-Rebeix Isabelle
Georgopoulos Costa
Ang Debbie
Nielsen Marit Nyholm
Davoine Claire-Sophie
Brice Alexis
Fontaine Bertrand
Gregersen Niels
Bross Peter
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