title: Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III.
abstract: BACKGROUND
  Spinal muscular atrophy (SMA type I, II and III) is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (SMN1). SMN2 is a centromeric copy gene that has been characterized as a major modifier of SMA severity. SMA type I patients have one or two SMN2 copies while most SMA type II patients carry three SMN2 copies and SMA III patients have three or four SMN2 copies. The SMN1 gene produces a full-length transcript (FL-SMN) while SMN2 is only able to produce a small portion of the FL-SMN because of a splice mutation which results in the production of abnormal SMNΔ7 mRNA.
  
  
  METHODS
  In this study we performed quantification of the SMN2 gene copy number in Russian patients affected by SMA type II and III (42 and 19 patients, respectively) by means of real-time PCR. Moreover, we present two families consisting of asymptomatic carriers of a homozygous absence of the SMN1 gene. We also developed a novel RT-qPCR-based assay to determine the FL-SMN/SMNΔ7 mRNA ratio as SMA biomarker.
  
  
  RESULTS
  Comparison of the SMN2 copy number and clinical features revealed a significant correlation between mild clinical phenotype (SMA type III) and presence of four copies of the SMN2 gene. In both asymptomatic cases we found an increased number of SMN2 copies in the healthy carriers and a biallelic SMN1 absence. Furthermore, the novel assay revealed a difference between SMA patients and healthy controls.
  
  
  CONCLUSIONS
  We suggest that the SMN2 gene copy quantification in SMA patients could be used as a prognostic tool for discrimination between the SMA type II and SMA type III diagnoses, whereas the FL-SMN/SMNΔ7 mRNA ratio could be a useful biomarker for detecting changes during SMA pharmacotherapy.
authors.affiliation: Laboratory for Prenatal Diagnostics of Inherited Diseases, Ott's Institute of Obstetrics and Gynecology RAMS, Mendeleevskaya line 3, Saint-Petersburg, Russia.
authors.forename: Galina Yu
authors.initials: GY
authors.lastname: Zheleznyakova
authors.forename: Anton V
authors.initials: AV
authors.lastname: Kiselev
authors.forename: Viktor G
authors.initials: VG
authors.lastname: Vakharlovsky
authors.forename: Mathias
authors.initials: M
authors.lastname: Rask-Andersen
authors.forename: Rohit
authors.initials: R
authors.lastname: Chavan
authors.forename: Anna A
authors.initials: AA
authors.lastname: Egorova
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
authors.forename: Vladislav S
authors.initials: VS
authors.lastname: Baranov
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012426:Russia; D017384:Sequence Deletion; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein