https://scholars.lib.ntu.edu.tw/handle/123456789/463677
標題: | PLA2G6 mutations in PARK14-linked young-onset parkinsonism and sporadic Parkinson's disease | 作者: | Lu C.-S Lai S.-C RUEY-MEEI WU Weng Y.-H Huang C.-L Chen R.-S Chang H.-C Wu-Chou Y.-H Yeh T.-H. |
公開日期: | 2012 | 卷: | 159 B | 期: | 2 | 起(迄)頁: | 183-191 | 來源出版物: | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | 摘要: | Mutations of PLA2G6 gene have been lately proposed to be the causative gene for PARK14 in patients with autosomal recessive young-onset parkinsonism (YOPD). The role of PLA2G6 mutations as a risk factor for Parkinson's disease is not clear. To study the PLA2G6 mutations in PARK14-linked patients and its association with the onset of sporadic Parkinson's disease (sPD), sequencing and gene dosage analyses were carried out in 25 patients (onset age ≦30 years) then the identified variants were assessed in 956 sporadic PD (sPD) patients and 802 age-matched healthy controls. Four genetic variants were identified; one patient had homozygous c.991G>T (p.Asp331Tyr) mutation, two had compound heterozygous c.991G>T/c.1077G>A (p.Met358IlefsX) mutation, one had single c.1976A>G (p.Asn659Ser) mutation, and one patient had an exon 1 hetero-deletion. The c.1077G>A mutation resulted in a 4-bp deletion in leukocyte mRNA by activating a cryptic splice site in exon 7. Only p.Asp331Tyr was identified in four sPD patients and four controls. The onset age for PLA2G6 mutation carriers was younger than that for sPD (29.86±8.59 vs. 56.84±11.33 years, P=0.0002). The analysis of previously reported PARK14 patients revealed that those who carried a truncated mutation tended to have a complicated phenotype and atrophies of cortex and cerebellum. In conclusion, PLA2G6 mutation was the second common genetic cause after PRKN mutation in our YOPD patients and might be a risk factor for early-onset PD in Han Chinese. Additionally, mutation data should be interpreted carefully because even a synonymous mutation could cause abnormal mRNA splicing. ? 2011 Wiley Periodicals, Inc. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/463677 | ISSN: | 1552-4841 | DOI: | 10.1002/ajmg.b.32012 | SDG/關鍵字: | peptides and proteins; protein PLA2G6; unclassified drug; adolescent; adult; article; brain cortex atrophy; cerebellum atrophy; child; controlled study; exon; female; frameshift mutation; gene dosage; gene mutation; gene sequence; genetic variability; homozygosity; human; male; missense mutation; nucleotide sequence; onset age; Parkinson disease; parkinsonism; phenotype; priority journal; school child; Adolescent; Adult; Age of Onset; Case-Control Studies; Child; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Group VI Phospholipases A2; Humans; Male; Mutation; Parkinsonian Disorders; Phenotype; Polymerase Chain Reaction; Ubiquitin-Protein Ligases; Young Adult |
顯示於: | 醫學系 |
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