title: Mutational screening of the mortalin gene (HSPA9) in Parkinson's disease.
abstract: Mortalin is a mitochondrial chaperone of the heat shock protein 70 family. Mortalin plays a central role in mitochondrial biogenesis through its capacity to direct the import of nuclear-encoded proteins into the mitochondria. As mitochondrial dysfunction has been involved in Parkinson's disease (PD), changes in mortalin function and expression could manifest as a higher risk of developing PD. In agreement with this, mortalin expression was decreased in the mitochondrial fraction of neurons from the substantia nigra of PD patients. We hypothesised that DNA variants in the mortalin gene (HSPA9) could contribute to the risk of developing PD. We analysed the 17 HSPA9 coding exons in 330 PD patients and 250 controls. In addition to several polymorphisms, found in patients and controls, three variants were found in 3 patients but none of the controls: two missense (R126 > W and P509 > S) and a 17 bp insertion in intron 8 (predicted to affect RNA splicing). Our study suggests that putative mutations in the mortalin, although rare, could contribute to the risk of developing PD.
authors: Genética Molecular, Hospital Central de Asturias-Maternidad, 33006, Oviedo, Spain.
authors: Lorena
authors: L
authors: De Mena
authors: Eliecer
authors: E
authors: Coto
authors: Elena
authors: E
authors: Sánchez-Ferrero
authors: René
authors: R
authors: Ribacoba
authors: Luis M
authors: LM
authors: Guisasola
authors: Carlos
authors: C
authors: Salvador
authors: Marta
authors: M
authors: Blázquez
authors: Victoria
authors: V
authors: Alvarez
mesh_terms: D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid
chemical_list: D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D024101:Mitochondrial Proteins