Unit:
Κατεύθυνση Βασική ΈρευναLibrary of the School of Health Sciences
Author:
Papagiannopoulou Georgia
Supervisors info:
Γεωργία Καραδήμα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Λεωνίδας Στεφανής, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μιχαήλ Κουτσιλιέρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Γενετική μελέτη του γονιδίου C9ORF72 σε Έλληνες ασθενείς με νόσο Parkinson ή άτυπα παρκινσονικά σύνδρομα
Translated title:
Analysis of C9ORF72 repeat expansions in Greek patients with Parkinson's disease or atypical parkinsonism
Summary:
Introduction: The C9ORF72 gene, located in the short arm of chromosome 9 (9p) encodes a protein, expressed in high percentage in the central nervous system, yet its function has not been clarified. A dynamic mutation (hexanucleotide GGGGCC repeat expansion) in the C9ORF72 gene has been studied extensively in Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, as well as in HD-like syndromes, compared to patients with Parkinson's disease and atypical parkinsonism syndromes. The aim of this study is to further investigate the frequency of the C9ORF72 gene mutations in Greek patients with Parkinson's disease or atypical parkinsonism and its association with their phenotypic profile.
Material and Methods: The study material included 91 DNA samples of patients with Parkinson's disease or atypical parkinsonism syndromes [75 patients with Parkinson's disease from a biobank from the Biomedical Research Foundation Academy of Athens (BRFAA), and 18 patients (2 with Parkinson's disease, 15 with Corticobasal Syndrome and 1 with Lewy Body Dementia) from the Neurogenetics Unit of the 1st Department of Neurology, “Eginition” Hospital, collected prospectively during the study (March 2022-March 2023)]. As a first step, genetic testing involved polymerase chain reaction (PCR), and the products were analyzed on agarose gel. The next step included repeat-primed PCR (RP-PCR), a technique designed to detect large numbers of repeat expansions. RP-PCR products were analyzed in an automated genetic analyzer and evaluated with appropriate software programs. Statistical analyses of the results were performed using R software version 3.5.0.
Results: In the study material of 91 patients (75 with Parkinson's disease, 15 with Corticobasal Syndrome and 1 with Lewy Body Dementia) no pathogenic or intermediate repeat expansion was detected in the C9ORF72 gene. Of these samples, RP-PCR was applied to 26 samples. Additionally, analysis revealed that the allele detected with the highest frequency was the allele with 3 repeats of the hexanucleotide GGGGCC (53%), and the next most frequently detected allele was the one with 9 repeats (14%).
Discussion: The results of the present study agree with those of international literature, in which pathogenic expansion in the C9ORF72 gene in patients with Parkinson's disease or atypical parkinsonism syndromes seems to be found very rarely or not at all. The advantages of the study include the contribution to the broader investigation of the role of the C9ORF72 gene in this group of patients as well as the increase of number of Greek patients with Parkinson's disease and atypical parkinsonism screened for pathogenic mutation in the C9ORF72 gene.
Main subject category:
Health Sciences
Keywords:
C9ORF72 repeat expansions, Parkinson's disease, Atypical parkinsonism, C9ORF72-related neurodegenerative diseases, Greek population
