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Friday, November 9, 2018

Mutations on NUS1 Gene Can Significantly Raise Person’s Risk of Parkinson’s, Study Reports

 NOVEMBER 9, 2018 BY ALICE MELÃO 


Mutations affecting the NUS1 gene are linked to a significantly increased risk — 11 times higher — of developing Parkinson’s disease, study shows.
Although exact triggers of Parkinson’s disease remain unclear, aging, and environmental and genetic factors are believed to be major culprits.
SNCA was the first gene to be linked to the development of Parkinson’s. Since its discovery in 1997, scientists have attempted to find other genes that may also play a role.
Chinese researchers conducted a detailed genetic analysis of samples collected from 39 patients with early-onset Parkinson’s disease, their parents, and 20 unaffected siblings, aiming to detect de novo mutations associated with the disease.
de novo mutation is a genetic alteration evident for the first time in one family member as a result of a mutation in the egg or sperm of a parent, or a mutation that arises in the fertilized egg itself during early development. A child with a de novo (new) mutation will develop the associated disease, while his parents or siblings will not.
Researchers identified 12 genes carrying de novo mutations — MAD1L1NUP98PPP2CBPKMYT1TRIM24CEP131CTTNBP2NUS1SMPD3MGRN1IFI35, and RUSC2. These genes are known to be expressed in two brain regions affected in Parkinson’s disease, called the stratum and substantia nigra, and could be functionally relevant to early-onset Parkinson’s.
Biologic network analysis showed that all the identified genes may share similar biological functions, and act together to increase the risk of developing Parkinson’s.
Patients did not have any other genetic variants previously associated with the disease.
Next, researchers explored the presence of rare mutations in these 12 genes in samples collected from 1,852 patients with sporadic (non-familial) Parkinson’s disease and 1,565 healthy volunteers. In this secondary screening, no significant alterations were found with exception of the NUS1 gene.
To confirm this finding, the team performed a detailed analysis of the NUS1 gene in a larger number of samples (3,237 patients and 2,858 controls). Similar to the previous analysis, Parkinson’s patients carried NUS1 mutations that were not present in the (healthy) control samples.
The presence of NUS1 variants, and consequent lower levels of the gene, were associated with a 11.3 times higher risk of having Parkinson’s disease.
Researchers also examined the role of the NUS1 gene in vivo, by deleting the equivalent gene — which shares 44% similarly with the human NUS1 — in a fly model (Drosophila). They observed that this deletion induced the loss of dopamine-producing nerve cells and, consequently, lower brain dopamine levels — two main hallmarks of Parkinson’s disease.
“These data … suggest that NUS1 plays important roles in dopamine neurons and that the loss of NUS1 could lead to neuronal dysfunction that is related to Parkinson’s disease,” the researchers wrote.
“[D]e novo mutations could contribute to early onset PD [Parkinson’s disease] pathogenesis and identify NUS1 as a candidate gene for PD,” they concluded.
https://parkinsonsnewstoday.com/2018/11/09/nus1-gene-mutations-linked-to-significantly-higher-risk-of-parkinsons-disease-in-study/

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