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Published on: April 4, 2018
Mutational screening of the mortalin gene (HSPA9) in Parkinson's disease
Lorena De Mena1, Eliecer Coto, Elena Sánchez-Ferrero
1Genética Molecular, Hospital Central de Asturias-Maternidad, 33006, Oviedo, Spain.
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.
Insights
DNA variants in the mortalin gene (HSPA9) may increase Parkinson's disease (PD) risk. Researchers found rare mutations in PD patients, suggesting mortalin's role in disease development.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Mortalin, a mitochondrial chaperone (heat shock protein 70 family), is crucial for mitochondrial biogenesis.
- Mitochondrial dysfunction is implicated in Parkinson's disease (PD).
- Reduced mortalin expression observed in PD patient neurons suggests a potential link.
Purpose of the Study:
- To investigate if DNA variants in the mortalin gene (HSPA9) contribute to Parkinson's disease risk.
- To explore the genetic association between HSPA9 and PD susceptibility.
Main Methods:
- Analyzed 17 HSPA9 coding exons in 330 PD patients and 250 controls.
- Screened for DNA variants, including polymorphisms and potential pathogenic mutations.
Main Results:
- Identified common polymorphisms in both patients and controls.
- Discovered three rare variants (two missense, one intronic insertion affecting splicing) exclusively in 3 PD patients.
Conclusions:
- Rare DNA variants in the mortalin (HSPA9) gene may represent a rare risk factor for developing Parkinson's disease.
- Further research is warranted to fully elucidate the role of mortalin variants in PD pathogenesis.
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