Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases

Neuromuscul Disord. 2018 Mar;28(3):208-215. doi: 10.1016/j.nmd.2018.01.003. Epub 2018 Jan 11.


Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by loss or mutations in SMN1. According to age of onset, achieved motor abilities, and life span, SMA patients are classified into type I (never sit), II (never walk unaided) or III (achieve independent walking abilities). SMN2, the highly homologous copy of SMN1, is considered the most important phenotypic modifier of the disease. Determination of SMN2 copy number is essential to establish careful genotype-phenotype correlations, predict disease evolution, and to stratify patients for clinical trials. We have determined SMN2 copy numbers in 625 unrelated Spanish SMA patients with loss or mutation of both copies of SMN1 and a clear assignation of the SMA type by clinical criteria. Furthermore, we compiled data from relevant worldwide reports that link SMN2 copy number with SMA severity published from 1999 to date (2834 patients with different ethnic and geographic backgrounds). Altogether, we have assembled a database with a total of 3459 patients to delineate more universal prognostic rules regarding the influence of SMN2 copy number on SMA phenotype. This issue is crucial in the present scenario of therapeutic advances with the perspective of SMA neonatal screening and early diagnosis to initiate treatments.

Keywords: Phenotype–genotype correlations; Prognosis considerations; SMN2 copies; Spinal muscular atrophy; Worldwide compilation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Copy Number Variations*
  • Databases, Genetic
  • Female
  • Gene Dosage
  • Genetic Association Studies*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Muscular Atrophy, Spinal / genetics*
  • Mutation
  • Phenotype
  • Prognosis
  • Spain
  • Survival of Motor Neuron 2 Protein / genetics


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