C9ORF72 repeat expansion is not associated with atypical parkinsonism in the Serbian population
Author:
Marjanovic Ana1ORCID, Dobricic Valerija2, Jecmenica-Lukic Milica1, Stankovic Iva1ORCID, Milicevic Ognjen3ORCID, Dragasevic-Miskovic Natasa1, Brankovic Marija1ORCID, Jankovic Milena4ORCID, Novakovic Ivana3ORCID, Svetel Marina1ORCID, Stefanova Elka1ORCID, Kostic Vladimir1ORCID
Affiliation:
1. Faculty of Medicine, University of Belgrade, Belgrade, Serbia + Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia 2. Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia + Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany 3. Faculty of Medicine, University of Belgrade, Belgrade, Serbia 4. Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia
Abstract
These include, among others, two forms of atypical Parkinsonism, multiple
system atrophy (MSA) and progressive supranuclear palsy (PSP). This study
aimed to assess the potential role of C9orf72 repeat expansions among
Serbian patients diagnosed with MSA and PSP. Genomic DNA of 44 MSA patients,
73 PSP patients, and 96 controls was extracted from peripheral blood, and
normal C9orf72 alleles were analyzed by standard quantitative fluorescence
polymerase chain reaction (QF-PCR) and fragment analysis. Subsequently, for
all samples presenting a single allele, repeat-primed PCR was performed with
two different sets of primers to avoid a false-negative result. Thirty
repeats were used as a pathogenic cut-off and 20-29 repeats for the
intermediate alleles. No pathological C9orf72 expansions were detected in
the MSA and PSP patients nor the control subjects. In the MSA group, the
most common was the allele with 2 repeats, and the largest repeat number was
14. Among PSP patients, the most common allele also had 2 repeats, while the
largest detected repeat size within the normal range was 17. Also, we
identified one PSP patient that had an intermediate size allele (25
repeats). We did not find correlation between the number of repeats and
disease onset, age at the time of examination, or disease duration in MSA or
PSP patients. Regarding family history, in PSP the sum of both allele
repeats numbers was higher in patients with positive family history than in
sporadic cases. The results presented in this study are the first systematic
assessment of C9orf72 allele sizes among patients diagnosed with MSA and PSP
in the Serbian population. Although the potential role of intermediate
C9orf72 repeats in neurodegenerative disorders is still to be elucidated,
our results support the current knowledge that C9orf72 repeat expansions are
not associated with MSA and PSP.
Funder
Ministry of Education, Science and Technological Development of the Republic of Serbia
Publisher
National Library of Serbia
Subject
Plant Science,Genetics
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