Population screening and cascade testing for carriers of SMA

Eur J Hum Genet. 2007 Jul;15(7):759-66. doi: 10.1038/sj.ejhg.5201821. Epub 2007 Mar 28.


Spinal muscular atrophy (SMA) is one of the most common autosomal-recessive diseases, caused by absence of both copies of the survival motor neuron 1 (SMN1) gene. Identification of SMA carriers has important implications for individuals with a family history and the general population. SMA carriers are completely healthy and most are unaware of their carrier status until they have an affected child. A total of 422 individuals have been studied to identify SMA carriers. This cohort included 117 parents of children homozygously deleted for SMN1 (94% were carriers and 6% had two copies of SMN1; of these individuals, two in seven had the '2+0' genotype, two in seven were normal but had children carrying a de novo deletion and three in seven were unresolved), 158 individuals with a significant family history of SMA (47% had one copy, 49% had two copies and 4% had three copies of SMN1) and 146 individuals with no family history of SMA (90% had two copies, 2% had one copy and 8% had three copies of SMN1). The SMA carrier frequency in the Australian population appears to be 1/49 and the frequency of two-copy SMN1 alleles and de novo deletion mutations are both at least 1.7%. A multimodal approach involving quantitative analysis, linkage analysis and genetic risk assessment (GRA), facilitates the resolution of SMA carrier status in individuals with a family history as well as individuals of the general population, providing couples with better choices in their family planning.

Publication types

  • Validation Study

MeSH terms

  • Australia / epidemiology
  • Cohort Studies
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Female
  • Gene Dosage
  • Gene Frequency
  • Genetic Carrier Screening / methods*
  • Genetic Linkage
  • Genetic Testing / methods*
  • Humans
  • Male
  • Muscular Atrophy, Spinal / diagnosis*
  • Muscular Atrophy, Spinal / genetics*
  • Nerve Tissue Proteins / genetics*
  • New Zealand / epidemiology
  • Polymerase Chain Reaction
  • RNA-Binding Proteins / genetics*
  • SMN Complex Proteins
  • Survival of Motor Neuron 1 Protein


  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein