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Srpski arhiv za celokupno lekarstvo 2018 Volume 146, Issue 11-12, Pages: 646-652
https://doi.org/10.2298/SARH180801069B
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SMN1 copy number as a modifying factor of survival in Serbian patients with sporadic amyotrophic lateral sclerosis

Brkušanin Miloš ORCID iD icon (Faculty of Biology, Center for Human Molecular Genetics, Belgrade)
Jeftović-Velkova Irena (School of Medicine, Clinical Center of Serbia, Neurology Clinic, Belgrade)
Jovanović Vladimir M. ORCID iD icon (Siniša Stanković Institute for Biological Research, Department of Genetic Research, Belgrade)
Perić Stojan ORCID iD icon (School of Medicine, Clinical Center of Serbia, Neurology Clinic, Belgrade)
Pešović Jovan ORCID iD icon (Faculty of Biology, Center for Human Molecular Genetics, Belgrade)
Brajušković Goran (Faculty of Biology, Center for Human Molecular Genetics, Belgrade)
Stević Zorica (School of Medicine, Clinical Center of Serbia, Neurology Clinic, Belgrade)
Savić-Pavićević Dušanka ORCID iD icon (Faculty of Biology, Center for Human Molecular Genetics, Belgrade)

Introduction/Objective. Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The majority of cases are apparently sporadic ALS (SALS) with variants in susceptibility genes or sometimes in high-risk ALS genes. Two ALS susceptibility genes are SMN1, whose functional loss causes spinal muscular atrophy (SMA), and a nearly identical SMN2 gene, which modulates SMA severity. In this study we examined the association of copy number variations (CNVs) of SMN1 and SMN2 genes and two additional genes, SERF1 and NAIP, residing in the same genomic region (i.e. 5q13.2 segmental duplication), with SALS in patients from Serbia. Methods. Multiplex ligation-dependent probe amplification was used to determine CNVs of each gene in a clinically well-characterised group of 153 Serbian SALS patients and 153 controls. Results. Individual association between SMN1, SMN2, SERF1 or NAIP CNVs and SALS susceptibility or survival was not found. Survival curves based on the multivariable Cox regression analysis showed that three SMN1 copies, lower ALS Functional Rating Scale Revised (ALSFRS-R) score at the time of diagnosis, faster decline of the ALSFRS-R score over time, and shorter diagnostic delay result in shorter survival of Serbian SALS patients. Conclusion. Clinical variables might be complemented with the SMN1 copy number to improve prediction of survival in Serbian SALS patients.

Keywords: survival motor neuron, amyotrophic lateral sclerosis, H4F5, NAIP, SMN1

Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173016