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01-12-2005 | Original Article

Differential expression of splice variant and wild-type parkin in sporadic Parkinson's disease

Authors: E. K. Tan, H. Shen, J. M. M. Tan, K. L. Lim, S. Fook-Chong, W. P. Hu, M. C. Paterson, V. R. Chandran, K. Yew, C. Tan, Y. Yuen, R. Pavanni, M. C. Wong, K. Puvan, Y. Zhao

Published in: Neurogenetics | Issue 4/2005

Abstract

Background

Altered splicing of parkin under cellular stress could lead to changes in gene expression and altered protein activity. The causative role of parkin in sporadic Parkinson's disease (PD) is unknown.

Objectives

We described a parkin splice variant (SV) in the substantia nigra and leukocytes of sporadic PD patients. Using a case control methodology, we investigated the exon 4 SV (E4SV) and wild-type parkin expression in the leukocytes of sporadic PD patients and healthy individuals.

Methods/Results

We identified a parkin E4SV in the substantia nigra and leukocytes of sporadic PD patients and controls by reverse transcriptase–polymerase chain reaction (PCR). The exon 4 (122 bp) deletion resulted in a reading frame shift over the junction of exons 3–5 and a stop codon (tga) 17 bp downstream from exon 3. The translated truncated protein was associated with a total loss of the two-RING finger functional domain. Utilizing TaqMan real-time PCR with probes located across the junction of exons 3–4 or 3–5, we demonstrated an over-expression of E4SV/wild-type parkin ratio in the leukocytes of sporadic PD patients compared to age-, gender-, and race-matched controls (p<0.0005). A multivariate regression analysis demonstrated that the ratio of E4SV/wild-type parkin expression increased with age in PD patients, but this was not observed in the controls (p<0.0005).

Conclusion

The relative expression of E4SV/wild type parkin was increased in sporadic PD compared to healthy controls. Based on our observations, further functional studies to determine the pathophysiologic role of E4SV in sporadic PD patients will be of importance.

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Title: Differential expression of splice variant and wild-type parkin in sporadic Parkinson's disease
Authors: E. K. Tan
H. Shen
J. M. M. Tan
K. L. Lim
S. Fook-Chong
W. P. Hu
M. C. Paterson
V. R. Chandran
K. Yew
C. Tan
Y. Yuen
R. Pavanni
M. C. Wong
K. Puvan
Y. Zhao
Publication date: 01-12-2005
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 4/2005
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-005-0001-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Differential expression of splice variant and wild-type parkin in sporadic Parkinson's disease

Abstract

Background

Objectives

Methods/Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objectives

Methods/Results

Conclusion

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