The role of SMN in spinal muscular atrophy

J Neurol. 2000 Mar:247 Suppl 1:I37-42. doi: 10.1007/s004150050555.

Abstract

Childhood spinal muscular atrophy (SMA) is a common autosomal recessive disorder which is characterized by muscle weakness due to degeneration of motoneurons in the spinal cord and brainstem nuclei. Positional cloning strategies have revealed several gene candidates including the genes for the survival motoneuron (SMN) and the neuronal apoptosis inhibitory protein (NAIP). Both genes are duplicated on chromosome 5. Homozygous deletions/mutations of the telomeric SMN gene, which is expressed from both copies on human chromosome 5, are associated with the disease. Recent reports suggest involvement of the SMN protein in the formation of spliceosomal particles in the cytoplasm and in the regeneration of spliceosomes in the nucleus. These data put spinal muscular atrophy into a growing group of disorders of RNA metabolism which also include fragile-X syndrome and myotonic dystrophy. Relevance of these previous data for the pathogenesis of the disease are discussed in this review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Survival
  • Child
  • Chromosomes, Human, Pair 5 / genetics*
  • Cyclic AMP Response Element-Binding Protein
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Knockout
  • Motor Neurons / pathology*
  • Nerve Tissue Proteins / genetics*
  • Point Mutation
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • Spinal Muscular Atrophies of Childhood / genetics*
  • Spinal Muscular Atrophies of Childhood / physiopathology

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • SMN Complex Proteins