[Spinal muscular atrophy: SMN protein deficiency]

Spinal muscular atrophy is a heterogeneous group of disorders characterised by the loss of alfa motor neurons in spinal cord. Autosomal recessive infantile and juvenile proximal spinal muscular atrophy is the most common form of the disease. The identification of the disease gene-Survival of Motor Neuron (SMN) was a major advance in understanding of the molecular basis of SMA. 98% of SMA patients show the homozygous absence of at least exon 7 telomeric copy of SMN, the rest carry small intragenic mutations, usually in exon 6. Two different mechanisms seem to be responsible for the absence of the telomeric copy: deletion in severe form and gene conversion associated with mild phenotype. Recently, biochemical studies resulted in identification of the 38kDa survival motor neuron (SMN) protein, probably involved in the biogenesis of spliceosomal snRNP. The SMN protein level was shown to be 100-fold reduced in spinal cord of SMA 1 patients.