Abstract
Mutations in HTRA2 have been reported to associate with Parkinson's disease (PD). This study investigates if the genetic variants in HTRA2 contribute to Taiwanese PD. HTRA2 cDNA fragments from 80 patients with early-onset PD (onset ≤50 years) were sequenced. The identified variants were further examined for a cohort of PD and ethnically matched controls. A novel heterozygous R36W was identified in one early-onset and two late-onset PD patients, which was absent in 606 normal controls. The clinical features and 99mTc-TRODAT-1 SPECT image of the early-onset patient carrying R36W were similar to that of idiopathic PD. The R36W mutation of the patient was inherited from his mother whose SPECT revealed asymmetric reduction of 99mTc-TRODAT-1 uptake in the left striatum, suggesting that the defect of the nigrostriatal pathway may be attributable to the R36W in this family. Protein subcellular fractionation further revealed that R36W affected the processing of the proprotein after transport into mitochondria. Although the functional assays are promising, a larger cohort of both cases and controls should be screened to clarify the role of R36W in Taiwanese PD pathogenicity.
| Original language | English |
|---|---|
| Pages (from-to) | 491-498 |
| Number of pages | 8 |
| Journal | Journal of Neural Transmission |
| Volume | 121 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2014 Jan 1 |
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Keywords
- HTRA2
- Mitochondrial localization
- Mutation screening
- Parkinson's disease
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Psychiatry and Mental health
- Biological Psychiatry
Cite this
HTRA2 variations in Taiwanese Parkinson's disease. / Chen, Chiung Mei; Wu, Chun Hsien; Hsieh, Chin Hsia; Lin, Chih Hsin; Chen, I. Cheng; Chen, Yi Chun; Lee, Li Ching; Lee, Chi Mei; Tseng, Yung-Che; Lee, Guey-Jen; Wu, Yih Ru.
In: Journal of Neural Transmission, Vol. 121, No. 5, 01.01.2014, p. 491-498.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HTRA2 variations in Taiwanese Parkinson's disease
AU - Chen, Chiung Mei
AU - Wu, Chun Hsien
AU - Hsieh, Chin Hsia
AU - Lin, Chih Hsin
AU - Chen, I. Cheng
AU - Chen, Yi Chun
AU - Lee, Li Ching
AU - Lee, Chi Mei
AU - Tseng, Yung-Che
AU - Lee, Guey-Jen
AU - Wu, Yih Ru
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Mutations in HTRA2 have been reported to associate with Parkinson's disease (PD). This study investigates if the genetic variants in HTRA2 contribute to Taiwanese PD. HTRA2 cDNA fragments from 80 patients with early-onset PD (onset ≤50 years) were sequenced. The identified variants were further examined for a cohort of PD and ethnically matched controls. A novel heterozygous R36W was identified in one early-onset and two late-onset PD patients, which was absent in 606 normal controls. The clinical features and 99mTc-TRODAT-1 SPECT image of the early-onset patient carrying R36W were similar to that of idiopathic PD. The R36W mutation of the patient was inherited from his mother whose SPECT revealed asymmetric reduction of 99mTc-TRODAT-1 uptake in the left striatum, suggesting that the defect of the nigrostriatal pathway may be attributable to the R36W in this family. Protein subcellular fractionation further revealed that R36W affected the processing of the proprotein after transport into mitochondria. Although the functional assays are promising, a larger cohort of both cases and controls should be screened to clarify the role of R36W in Taiwanese PD pathogenicity.
AB - Mutations in HTRA2 have been reported to associate with Parkinson's disease (PD). This study investigates if the genetic variants in HTRA2 contribute to Taiwanese PD. HTRA2 cDNA fragments from 80 patients with early-onset PD (onset ≤50 years) were sequenced. The identified variants were further examined for a cohort of PD and ethnically matched controls. A novel heterozygous R36W was identified in one early-onset and two late-onset PD patients, which was absent in 606 normal controls. The clinical features and 99mTc-TRODAT-1 SPECT image of the early-onset patient carrying R36W were similar to that of idiopathic PD. The R36W mutation of the patient was inherited from his mother whose SPECT revealed asymmetric reduction of 99mTc-TRODAT-1 uptake in the left striatum, suggesting that the defect of the nigrostriatal pathway may be attributable to the R36W in this family. Protein subcellular fractionation further revealed that R36W affected the processing of the proprotein after transport into mitochondria. Although the functional assays are promising, a larger cohort of both cases and controls should be screened to clarify the role of R36W in Taiwanese PD pathogenicity.
KW - HTRA2
KW - Mitochondrial localization
KW - Mutation screening
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=84901262991&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901262991&partnerID=8YFLogxK
U2 - 10.1007/s00702-013-1131-9
DO - 10.1007/s00702-013-1131-9
M3 - Article
C2 - 24337630
AN - SCOPUS:84901262991
VL - 121
SP - 491
EP - 498
JO - Journal of Neural Transmission
JF - Journal of Neural Transmission
SN - 0300-9564
IS - 5
ER -