title: Application of a rapid non-invasive technique in the molecular diagnosis of spinal muscular atrophy (SMA).
abstract: OBJECTIVE
  Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by mutations of the SMN1 gene. The most frequent mutation is biallelic deletion of exon 7 of the SMN1 gene. A small percentage of SMA patients present compound heterozygosity with a point mutation on one allele and deletion on the other. In the remaining cases the disease is unlikely to be related to SMN1 defects. The aim of our study was to estimate the frequency of the common biallelic exon 7 SMN1 deletion in our Polish SMA cohort and implement a test for assessing a molecular defect at the SMN1 locus versus defects in the other genes.
  
  
  METHODS
  The molecular analysis was performed in a group of 269 patients fulfilling diagnostic criteria of the International SMA Consortium. The common SMN1 exon 7 deletion was tested by a standard PCR analysis. Patients lacking the common mutation were subsequently analyzed for a number of SMN1 alleles with a quantitative test based on real-time PCR.
  
  
  RESULTS
  The frequency of homozygous loss of exon 7 in the SMN1 gene was 96.6% (260/269) in our Polish SMA cohort. In 5 of 9 non-deleted patients the real-time PCR analysis showed a decreased number of SMN1 copies. We anticipate that the non-deleted allele carries a second mutation in SMN1 which may contribute to the pathogenesis of SMA. We have also identified 4 patients (1.5%) with SMA carrying two SMN1 alleles without the exon 7 deletion.
  
  
  CONCLUSIONS
  The molecular analysis of the biallelic exon 7 of the SMN1 deletion is a standard and reliable test in cases of SMA. Introduction of a quantitative test based on "real-time PCR" further enhances the diagnostic potential by increasing the detection rate of cases likely to be caused by point mutation of the SMN1 gene.
authors.affiliation: Neuromuscular Unit, Medical Research Centre, Polish Academy of Science, Warsaw. mariaj@cmdik.pan.pl
authors.forename: Maria
authors.initials: M
authors.lastname: Jedrzejowska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wiszniewski
authors.forename: Janusz
authors.initials: J
authors.lastname: Zimowski
authors.forename: Anna
authors.initials: A
authors.lastname: Kostera-Pruszczyk
authors.forename: Barbara
authors.initials: B
authors.lastname: Ryniewicz
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bal
authors.forename: Jacek
authors.initials: J
authors.lastname: Zaremba
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Mazurczak
authors.forename: Irena
authors.initials: I
authors.lastname: Hausmanowa-Petrusewicz
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000453:epidemiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017354:Point Mutation; D011044:Poland / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins / Q000378:metabolism*; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 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; D055533:Survival of Motor Neuron 1 Protein