Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Genetics
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To investigate the genetic etiology of early-onset (AAO > 45 Years) parkinsonism.
Background: Parkinsonism is a neurological syndrome characterized by resting tremor, rigidity, bradykinesia and postural instability. Although Parkinson’s disease (PD) is the most frequent cause, a range of neurological conditions may present a similar set of symptoms, and early on in the disease, different forms of parkinsonism have greater overlap. Mutations in PRKN, PINK1, and DJ-1 causes a mild and slowly progressive early-onset disease, whereas mutations in ATP13A2, PLA2G6, FBXO7, DNAJC6 and SYNJ1 causes early/juvenile-onset atypical parkinsonism with additional clinical signs. Interestingly, proteins of aforementioned genes are important for mitochondrial maintenance and lysosomal degradation.
Methods: We studied 105 early-onset parkinsonism [Mean AAO = 39.3 ± 5.0 years] patients from Norway. Exon-dosage analyses, whole-exome sequencing and genome-wide genotyping were performed. Analysis of the data, under a recessive model, was done by: i) Describing variability in genes previously described in parkinsonism, ii) genetic components of nominated cellular pathways, and iii) mapping novel genes within shared runs of homozygosity (ROH).
Results: Patients had slowly progressive motor symptoms and were generally cognitively spared
Characteristic | Total (n=105) |
Gender ratio (M:F) | 1.6:1 |
Age at study (y) | |
Mean ± SD | 60.1 ± 11.2 |
Range | 28-87 |
Age at onset (y) | |
Mean ± SD | 39.1 ± 5.1 |
Range | 22-45 |
UPDRS stage III at 10 years of disease | |
Mean ± SD | 24.8 ± 12.1 |
Range | 4-65 |
Hoehn & Yahr at 10 years of disease | |
Mean ± SD | 2.6 ± 0.9 |
Range | 1-5 |
MoCA at 15 years of disease | |
Mean ± SD | 25.5 ± 4.1 |
Conclusions: There is a significant genetic component in the etiology of early-onset parkinsonism. Here we describe ∼12% of early-onset parkinsonism patients with mutations in genes previously implicated in disease. Additionally, we have found variability in genes involved in mitochondrial maintenance and lysosomal degradation. Unraveling of the genetic etiology and description of their clinical phenotype is of great benefit in distinguishing multiple disorders which present parkinsonism at early stages, as making an accurate and early diagnosis of such disorders is challenging.
To cite this abstract in AMA style:
E.K. Gustavsson, J. Trinh, M. McKenzie, S. Bortnick, J.O. Aasly, M.J. Farrer. Genetic Identification of early-onset parkinsonism among Norwegian patients [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/genetic-identification-of-early-onset-parkinsonism-among-norwegian-patients/. Accessed September 7, 2024.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-identification-of-early-onset-parkinsonism-among-norwegian-patients/