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Evaluating LRRK2 Genetic Variants with Unclear Pathogenicity
Joint Authors
Refai, Fathima Shaffra
Ng, Shin Hui
Tan, Eng King
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-6, 6 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-03-02
Country of Publication
Egypt
No. of Pages
6
Main Subjects
Abstract EN
Mutations in the leucine-rich repeat kinase 2 (LRRK2) have been known to be a major genetic component affecting Parkinson’s disease (PD).
However, the pathogenicity of many of the LRRK2 variants is unclear because they have been detected in single patients or also in patients and controls.
Here, we selected 5 exonic variants (L1165P, T1410M, M1646T, L2063X, and Y2189C) from each of the protein domain of LRRK2 and analysed their possible association with pathogenicity using in vitro functional assays.
Point mutations representing each of these variants were incorporated into the LRRK2 gene, and functional aspects such as the percentage of cell survival upon application of stress and kinase activity were measured.
Our results showed that all 5 variants had a significantly negative effect on the survival of cells, in both presence and absence of stress, as compared to the wild-type.
In addition, there was also a slight increase in kinase activity in most of the variants in comparison to the wild-type.
A negative correlation between cell survival and kinase activity was observed.
These data suggest that most of the variants despite being located in different domains of LRRK2 appear to exert a potential pathogenic effect possibly through an increased kinase activity, supporting a gain of function mechanism.
American Psychological Association (APA)
Refai, Fathima Shaffra& Ng, Shin Hui& Tan, Eng King. 2015. Evaluating LRRK2 Genetic Variants with Unclear Pathogenicity. BioMed Research International،Vol. 2015, no. 2015, pp.1-6.
https://search.emarefa.net/detail/BIM-1056356
Modern Language Association (MLA)
Refai, Fathima Shaffra…[et al.]. Evaluating LRRK2 Genetic Variants with Unclear Pathogenicity. BioMed Research International No. 2015 (2015), pp.1-6.
https://search.emarefa.net/detail/BIM-1056356
American Medical Association (AMA)
Refai, Fathima Shaffra& Ng, Shin Hui& Tan, Eng King. Evaluating LRRK2 Genetic Variants with Unclear Pathogenicity. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-6.
https://search.emarefa.net/detail/BIM-1056356
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1056356