New approaches in molecular diagnosis and population carrier screening for spinal muscular atrophy

Genet Test Mol Biomarkers. 2011 May;15(5):319-26. doi: 10.1089/gtmb.2010.0164. Epub 2011 Feb 17.


Autosomal recessive spinal muscular atrophy, the leading genetic cause of infant death, is due to loss of functional SMN1 genes, mainly as a result of homozygous deletions. Carrier frequency in the general population varies widely from 1/50 to 1/125 and has significant counseling implications. In a cohort of 210 patients with spinal muscular atrophy confirmed at the molecular level, 91.9% had a homozygous deletion and 14 were compound heterozygotes. Two novel point mutations were detected (c.524delC and c.734dupC) and the 11 bp duplication c.770_780dup was found at a high frequency. We describe the development of a simple and robust method for homozygous deletion detection, which enabled us to simplify the diagnostic workup. Further, carrier frequency in our population was established by direct quantification with the commercially available MLPA kit, following optimization for the use of dried blood spots as sample specimens.

Publication types

  • Evaluation Study

MeSH terms

  • Exons / genetics
  • Gene Frequency
  • Genetic Carrier Screening*
  • Genetic Testing / methods*
  • Genotype
  • Homozygote
  • Humans
  • Muscular Atrophy, Spinal / diagnosis*
  • Muscular Atrophy, Spinal / genetics*
  • Point Mutation
  • Polymerase Chain Reaction / methods
  • Portugal
  • Reagent Kits, Diagnostic
  • Sequence Deletion
  • Survival of Motor Neuron 1 Protein / genetics*


  • Reagent Kits, Diagnostic
  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein