New, Improved Version of the mCOP-PCR Screening System for Detection of Spinal Muscular Atrophy Gene (SMN1) Deletion

Kobe J Med Sci. 2017 Sep 7;63(2):E37-E40.

Abstract

Background: Spinal muscular atrophy (SMA) is a frequent autosomal recessive disorder, characterized by lower motor neuron loss in the spinal cord. More than 95% of SMA patients show homozygous survival motor neuron 1 (SMN1) deletion. We previously developed a screening system for SMN1 deletion based on a modified competitive oligonucleotide priming-PCR (mCOP-PCR) technique. However, non-specific amplification products were observed with mCOP-PCR, which might lead to erroneous interpretation of the screening results.

Aim: To establish an improved version of the mCOP-PCR screening system without non-specific amplification.

Methods: DNA samples were assayed using a new version of the mCOP-PCR screening system. DNA samples had already been genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP), showing the presence or absence of SMN1 exon 7. The new mCOP-PCR method contained a targeted pre-amplification step of the region, including an SMN1-specific nucleotide, prior to the mCOP-PCR step. mCOP-PCR products were electrophoresed on agarose gels.

Results: No non-specific amplification products were detected in electrophoresis gels with the new mCOP-PCR screening system.

Conclusion: An additional targeted pre-amplification step eliminated non-specific amplification from mCOP-PCR screening.

Keywords: spinal muscular atrophy; targeted pre-amplification; SMN1; SMN2; mCOP-PCR.

MeSH terms

  • Base Sequence
  • Case-Control Studies
  • Child
  • DNA / blood
  • DNA / genetics
  • DNA Primers / genetics
  • Gene Deletion*
  • Homozygote
  • Humans
  • Mass Screening
  • Polymerase Chain Reaction / methods*
  • Spinal Muscular Atrophies of Childhood / diagnosis
  • Spinal Muscular Atrophies of Childhood / genetics
  • Survival of Motor Neuron 1 Protein / genetics*
  • Survival of Motor Neuron 2 Protein / genetics

Substances

  • DNA Primers
  • SMN1 protein, human
  • SMN2 protein, human
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein
  • DNA