Association between SMN2 copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene

Marija Žarkov; Aleksandra Stojadinović; Slobodan Sekulić; Iva Barjaktarović; Olivera Stojiljković; Stojan Perić; Goran Keković; Biljana Drašković; Zorica Stević

doi:10.2298/5791

Marija Žarkov Neurology Clinic, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Aleksandra Stojadinović Child and Youth Health Care Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Slobodan Sekulić Neurology Clinic, Clinical Center of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia
Iva Barjaktarović Center for Forensic Medicine, Toxicology and Molecular Genetics, Clinical Center of Vojvodina, Novi Sad, Serbia
Olivera Stojiljković Department of Neurology, General Hospital Subotica, Serbia
Stojan Perić Neurology Clinic, Clinical Center of Serbia, Medical Faculty, University of Belgrade, Belgrade, Serbia
Goran Keković Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
Biljana Drašković Child and Youth Health Care Institute of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia
Zorica Stević Neurology Clinic, Clinical Center of Serbia, Medical Faculty, University of Belgrade, Belgrade, Serbia

DOI: https://doi.org/10.2298/5791

Keywords: muscular atrophy, spinal, genetic diseases, inborn, chromosome aberations, serbia,

Abstract

Aim: The aim of this paper was to determine association between SMN2 gene copy number and disease phenotype of Serbian spinal muscular atrophy (SMA) patients with homozygous deletion of exon 7 of the SMN1 gene. Methods: Patients were identified using regional Serbian hospital databases. Investigated clinical characteristics of the disease were: patients’ gender, age at disease onset, achieved and current developmental milestones, disease duration, current age, and the presence of the spinal deformities and joint contractures. Number of SMN1 and SMN2 gene copies was determined using real time PCR. Results: Among 43 identified patients, 37 (86.0%) showed homozygous deletion of SMN1 exon 7. One (2.7%) of 37 patients had SMA type I with 3 SMN2 copies, 11 (29.7%) patients had SMA type II with 3.1±0.7 copies, 17 (45.9%) patients had SMA type III with 3.7±0.9 copies, while 8 (21.6%) patients had SMA type IV with 4.2±0.9 copies. There were progressive increase in the SMN2 gene copy number from type II towards type IV (p<0.05). Higher SMN2 gene copy number was associated with better current motor performance (p<0.05). Conclusion: In Serbian patients with SMA, higher SMN2 gene copy number correlated with less severe disease phenotype. Possible effect of other phenotype modifiers should not be neglected.

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