title: Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene.
abstract: OBJECTIVE
  Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of alpha motor neurons in the spinal cord and the medulla oblongata, causing progressive muscle weakness and atrophy. The aim of this study was to determine association between the SMN2 gene copy number and disease phenotype in Serbian patients with SMA with homozygous deletion of exon 7 of the SMN1 gene.
  
  
  METHODS
  The 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. The number of SMN1 and SMN2 gene copies was determined using real-time polymerase chain reaction (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 was a progressive increase in the SMN2 gene copy number from type II towards type IV (p < 0.05). A higher SMN2 gene copy number was associated with better current motor performance (p < 0.05).
  
  
  CONCLUSIONS
  In the Serbian patients with SMA, a higher SMN2 gene copy number correlated with less severe disease phenotype. A possible effect of other phenotype modifiers should not be neglected.
authors.forename: Marija
authors.initials: M
authors.lastname: Zarkov
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stojadinović
authors.forename: Slobodan
authors.initials: S
authors.lastname: Sekulić
authors.forename: Iva
authors.initials: I
authors.lastname: Barjaktarović
authors.forename: Stojan
authors.initials: S
authors.lastname: Perić
authors.forename: Goran
authors.initials: G
authors.lastname: Keković
authors.forename: Biljana
authors.initials: B
authors.lastname: Drasković
authors.forename: Zorica
authors.initials: Z
authors.lastname: Stević
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005091:Exons; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D009043:Motor Activity; D009046:Motor Neurons / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D055771:Serbia; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics; D055815:Young Adult
chemical_list: C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein