title: [Quantitative analysis of SMN2 based on real-time PCR: correlation of clinical severity and SMN2 gene dosage].
abstract: Spinal muscular atrophy (SMA) is a common autosomal recessive disorder, caused by homozygous deletion of the survival motor neuron gene 1 (SMN1). SMN2, a gene highly homologous to SMN1, is considered to influence the severity of SMA. Patients with SMA have been classified into three types on the basis of age at onset and clinical severity. In the present study, we performed a quantitative analysis of SMN2 in 22 patients of SMA to further clarify the correlation between clinical severity and SMN2 gene dosage. We determined the SMN2 gene copy number based on real-time PCR. In 3 Type I patients with only one SMN2 copy, the clinical phenotype was the severest. The remaining 14 Type I patients had two or three copies of the SMN2 gene, and showed a variable clinical severity. A patient with 3 copies required artificial ventilation at 2 months old. Five Type II and Type III patients had at least 4 copies of the SMN2 gene. Although the SMN2 gene dosage correlates the clinical severity, the mechanism by which SMN2 shows compensation in some Type I patients remains to be determined.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, The University of Tokyo. makisaito-tky@umin.ac.jp
authors.forename: Makiko
authors.initials: M
authors.lastname: Saito
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Chen
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D016601:RNA-Binding Proteins / Q000235:genetics*; D055532:SMN Complex Proteins; D012720:Severity of Illness Index; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein