title: A novel mutation in the HSPD1 gene in a patient with hereditary spastic paraplegia.
abstract: A mutation in the HSPD1 gene has previously been associated with an autosomal dominant form of spastic paraplegia in a French family. HSPD1 encodes heat shock protein 60, a molecular chaperone involved in folding and quality control of mitochondrial proteins. In the present work we have investigated 23 Danish index patients with hereditary spastic paraplegia (HSP) for mutations in the HSPD1 gene. One patient was found to be heterozygous for a c.1381C > G missense mutation encoding the mutant heat shock protein 60 p.Gln461Glu. The mutation was also present in two unaffected brothers, but absent in 400 unrelated Danish individuals. We found that the function of the p.Gln461Glu heat shock protein 60 was mildly compromised. The c.1381C > G mutation likely represents a novel low-penetrance HSP allele.
authors.affiliation: Research Unit for Molecular Medicine, Faculty of Health Sciences Aarhus University Hospital , Skejby Sygehus, Brendstrupgaardsvej, 8200, Aarhus N, Denmark, jakob.hansen@ki.au.dk.
authors.forename: Jakob
authors.initials: J
authors.lastname: Hansen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Svenstrup
authors.forename: Debbie
authors.initials: D
authors.lastname: Ang
authors.forename: Marit N
authors.initials: MN
authors.lastname: Nielsen
authors.forename: Jane H
authors.initials: JH
authors.lastname: Christensen
authors.forename: Niels
authors.initials: N
authors.lastname: Gregersen
authors.forename: Jørgen E
authors.initials: JE
authors.lastname: Nielsen
authors.forename: Costa
authors.initials: C
authors.lastname: Georgopoulos
authors.forename: Peter
authors.initials: P
authors.lastname: Bross
mesh_terms: D000368:Aged; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics*; D003718:Denmark; D005192:Family Health; D005260:Female; D018698:Glutamic Acid / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins; D020125:Mutation, Missense / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D018834:Chaperonin 60; C060293:HSPD1 protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D005973:Glutamine; D018698:Glutamic Acid; D018833:Chaperonins