The frequency of SMN gene variants lacking exon 7 and 8 is highly population dependent

PLoS One. 2019 Jul 24;14(7):e0220211. doi: 10.1371/journal.pone.0220211. eCollection 2019.

Abstract

Spinal Muscular Atrophy (SMA) is a disorder characterized by the degeneration of motor neurons in the spinal cord, leading to muscular atrophy. In the majority of cases, SMA is caused by the homozygous absence of the SMN1 gene. The disease severity of SMA is strongly influenced by the copy number of the closely related SMN2 gene. In addition, an SMN variant lacking exons 7 and 8 has been reported in 8% and 23% of healthy Swedish and Spanish individuals respectively. We tested 1255 samples from the 1000 Genomes Project using a new version of the multiplex ligation-dependent probe amplification (MLPA) P021 probemix that covers each SMN exon. The SMN variant lacking exons 7 and 8 was present in up to 20% of individuals in several Caucasian populations, while being almost completely absent in various Asian and African populations. This SMN1/2Δ7-8 variant appears to be derived from an ancient deletion event as the deletion size is identical in 99% of samples tested. The average total copy number of SMN1, SMN2 and the SMN1/2Δ7-8 variant combined was remarkably comparable in all populations tested, ranging from 3.64 in Asian to 3.75 in African samples.

MeSH terms

  • Cells, Cultured
  • DNA Copy Number Variations
  • Ethnicity / genetics
  • Ethnicity / statistics & numerical data
  • Exons / genetics
  • Female
  • Gene Frequency
  • Genetics, Population
  • Geography
  • Humans
  • Male
  • Muscular Atrophy, Spinal / epidemiology*
  • Muscular Atrophy, Spinal / genetics*
  • Polymorphism, Genetic
  • Sequence Deletion
  • Survival of Motor Neuron 1 Protein / genetics*
  • Survival of Motor Neuron 2 Protein / genetics

Substances

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

Grants and funding

The author(s) received no specific funding for this work. RV, RS, MC, AGM, MR, MZ, NM, RB, RY, RK, SS, SL are employees at MRC Holland. JS is owner of MRC Holland. MRC Holland provided support in the form of salaries for authors and employees of MRC Holland RV, RS, MC, AGM, MR, MZ, NM, RB, RY, RK, SS, SL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. JS (the owner of MRC Holland) played a role in study design, decision to publish and preparation of the manuscript.