title: Mortalin mutations are not a frequent cause of early-onset Parkinson disease.
abstract: Dysfunctional mitochondria and the mitochondrial chaperone mortalin (HSPA9, GRP75) have been implicated in the pathogenesis of Parkinson disease (PD). We screened 139 early-onset PD (EOPD) patients for mutations in mortalin revealing one missense change (p.L358P) that was absent in 279 control individuals. We also found one additional missense variant among the controls (p.T333K). Although both missense changes were predicted to be disease causing, we detected no differences in subcellular localization, mitochondrial morphology, or respiratory function between wild-type and mutant mortalin. These findings suggest that variants in mortalin (1) are not a major cause of EOPD; (2) occur in patients and controls; and (3) do not lead to functional impairment of mitochondria.
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Freimann
authors.forename: Katja
authors.initials: K
authors.lastname: Zschiedrich
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.forename: Anne
authors.initials: A
authors.lastname: Grünewald
authors.forename: Heike
authors.initials: H
authors.lastname: Pawlack
authors.forename: Johann
authors.initials: J
authors.lastname: Hagenah
authors.forename: Katja
authors.initials: K
authors.lastname: Lohmann
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Ana
authors.initials: A
authors.lastname: Westenberger
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009447:Neuroblastoma / Q000473:pathology; D010101:Oxygen Consumption / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D014162:Transfection; D055815:Young Adult
chemical_list: D018840:HSP70 Heat-Shock Proteins; C080352:mortalin
keywords: Early-onset Parkinson disease; GRP75; HSPA9; Mitochondria; Mortalin