Summary We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Parkinsonism (ETP)) and 1144 controls using a repeat-primed PCR assay. We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk. However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls. Overall, 14 cases (13 PD, 1 ETP) and three controls had >20 repeat copies (Fisher's exact test p = 0.002).
Further, seven cases and no controls had >23 repeat copies ( p = 0. G2 Driving Test Tips Downsview. 003). Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP.
This also suggests that PD, ALS and FTD share some pathophysiological mechanisms of disease. Further studies are needed to elucidate the contribution of the C9ORF72 repeat in the overall PD population and to determine whether other common genetic risk factors exist between these neurodegenerative disorders. • • Introduction Parkinson disease (PD) is a neurodegenerative movement disorder characterized by bradykinesia, rigidity, postural instability and tremor. PD prevalence increases with age, with estimates of 4–5% of the population being affected at 85 years and older (Fahn,; Tansey et al., ). While the diagnosis of “idiopathic” PD is well established, there are many disorders that contain the essential elements of the PD phenotype, often termed Parkinsonism, such as progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Wider overlap also occurs, including frontotemporal dementia with Parkinsonism (FTDP-17) and Lewy Body Dementia (Wszolek et al., ). However, minimal clinical overlap has been reported between PD and amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by progressive muscular paralysis reflecting degeneration of the motor neuron in the primary motor cortex, brainstem and spinal cord (Wijesekera and Leigh, ).
Previous observations have linked Parkinsonism with motor neuron disease (Brait–Fahn disease) or the Guam PD-ALS-dementia complex. This raised the hypothesis that ALS and PD might be related, as members of a spectrum of phenotypes with shared pathophysiological elements (Brait et al.,; Uitti et al.,; Williams et al.,; Qureshi et al.,; Pinkhardt et al., ). However, consumption of the unusual amino acid BAA has subsequently been thought to be the cause of Guam PD-ALS-dementia, and the incidence of the disorder in Guam has dropped since dietary modifications (Khabazian et al.,; Pablo et al., ). Nonetheless, recently, a study has shown that rare genetic variants in the Angiogenin gene ( ANG) contribute to the occurrence of both PD and ALS (van Es et al., ). Mutations in the Valosin Containing Protein gene ( VCP) are linked with ALS and also have been postulated to be a risk factor for PD, though data reported to date are inconsistent (Johnson et al.,; Chan et al.,; Majounie et al., ). This raised the hypothesis that these two disorders share other common genes or pathways that contribute to the development of neurodegeneration. 1950 Minghi Torrent more. Therefore, when several reports recently demonstrated that large expansions of a hexanucleotide repeat in C9ORF72 were correlated with the development of ALS (Renton et al.,; DeJesus-Hernandez et al.,; Gijselinck et al., ), we set out to examine the involvement of this complex repeat in PD.
Aug 13, 2017 Dangers of Statin Drugs: What You Haven’t Been Told About Popular Cholesterol-Lowering Medicines. Hisense U2 Usb Driver. June 14, 2004 By Sally Fallon and Mary G. Enig, PhD 70 Comments. Official Full-Text Paper (PDF): Individualized current-shaping reduces DBS-induced dysarthria in patients with essential tremor. To investigate in patients with essential tremor (ET) treated with thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced dysarthria (SID). We waited at least 5 minutes.