title: HTRA2 variations in Taiwanese Parkinson's disease.
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.
authors: Department of Neurology, Chang Gung Memorial Hospital, Chang-Gung University College of Medicine, 199 Tung Hwa North Road, Taipei, 10507, Taiwan.
authors: Chiung-Mei
authors: CM
authors: Chen
authors: Chun-Hsien
authors: CH
authors: Wu
authors: Chin-Hsia
authors: CH
authors: Hsieh
authors: Chih-Hsin
authors: CH
authors: Lin
authors: I-Cheng
authors: IC
authors: Chen
authors: Yi-Chun
authors: YC
authors: Chen
authors: Li-Ching
authors: LC
authors: Lee
authors: Chi-Mei
authors: CM
authors: Lee
authors: Yung-Che
authors: YC
authors: Tseng
authors: Guey-Jen
authors: GJ
authors: Lee-Chen
authors: Yih-Ru
authors: YR
authors: Wu
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging; D003342:Corpus Striatum / Q000000981:diagnostic imaging; D005260:Female; D007839:Functional Laterality; D015870:Gene Expression; D014644:Genetic Variation; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport; D011877:Radionuclide Imaging; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics*; D013624:Taiwan
chemical_list: D024101:Mitochondrial Proteins; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2