The role of SMN in spinal muscular atrophy

Childhood spinal muscular atrophy (SMA) is a common autosomal recessive dis order which is characterized by muscle weakness due to degeneration of moto neurons in the spinal cord and brainstem nuclei. Positional cloning strateg ies have revealed several gene candidates including the genes for the survi val motoneuron (SMN) and the neuronal apoptosis inhibitory protein (NAIP). Both genes are duplicated on chromosome 5. Homozygous deletions/mutations o f the telomeric SMN gene, which is expressed from both copies on human chro mosome 5, are associated with the disease. Recent reports suggest involveme nt of the SMN protein in the formation of spliceosomal particles in the cyt oplasm and in the regeneration of spliceosomes in the nucleus. These data p ut spinal muscular atrophy into a growing group of disorders of RNA metabol ism which also include fragile-X syndrome and myotonic dystrophy. Relevance of these previous data for the pathogenesis of the disease are discussed i n this review.