C9orf72 genetic screening in amyotrophic lateral sclerosis patients from Serbia
Author:
Marjanovic Ana1, Palibrk Aleksa2, Dobricic Valerija3, Milicevic Ognjen4, Brankovic Marija1, Viric Vanja2, Drinic Aleksandra5, Mandic-Stojmenovic Gorana1, Jankovic Milena2, Basta Ivana1, Peric Stojan1, Novakovic Ivana1, Stefanova Elka1, Stevic Zorica1
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 3. Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia + Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany 4. Faculty of Medicine, University of Belgrade, Belgrade, Serbia, 5. Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
Abstract
Hexanucleotide repeats expansion in the C9orf72 gene is the most common cause
of familial and sporadic amyotrophic lateral sclerosis (ALS) cases in
Europe. In this study we aimed to determine the size and distribution of
C9orf72 alleles, and investigate the possible association of the repeat size
with several clinical parameters in ALS patients from Serbia. Patients were
recruited from 2011-2021 and analysed using fragment length analysis and
Southern blot. Out of 383 ALS patients, we have detected 31 (8.09%) patients
with repeat expansion. In the total ALS cohort, clinical overlap with
frontotemporal dementia (FTD) was registered in 17 (4.44%) patients, and
among them, 5 (29.41%) were expansion carriers. There was no difference in
the age of onset, age at the examination or disease duration, gender, and
the frequency of spinal and bulbar onset between patients with and without
C9orf72 expansion. The presence of positive family history (34.48% vs.
15.65%) and FTD (16.13% vs. 3.41%) was more frequent in expansion-positive
vs. expansion-negative patients. In expansion-positive patients,
significantly higher values of the largest detected repeat were found in
patients with ALS in the family, and in expansion-negative, a higher median
value of the smaller allele was noted in patients with a positive family
history of ALS, dementia, and both in comparison to the rest of the group. A
correlation of the repeat size was not found with the age of onset in both
patients with and without the expansion. This is the first detailed study of
C9orf72 sizing in ALS patients from Serbia. Our results emphasize the need
for C9orf72 genetic screening in ALS patients with/without FTD.
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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