Perspectives and diagnostic considerations in spinal muscular atrophy

Spinal muscular atrophy is an autosomal recessive neurode-enerative disease and the most common genetic cause of infant mortality. The disease results in motor neuron loss and skeletal muscle atrophy. Spinal muscular atrophy is caused by mutations in the telomeric copy of the survival motor neuron 1 (SMN1) gene, but all patients retain a centromeric copy of the gene, SMN2. In the majority of cases, the disease severity correlates inversely with an increased SMN2 gene copy number. Because spinal muscular atrophy is both a severe and common disorder, a direct carrier testing has been beneficial to many families. The survival motor neuron protein is ubiquitously expressed and performs a role in the assembly of the spliceosome. It is still not understood why mutations in the SMN1 gene only seem to affect motor neurons. Progress has been made by developing therapeutic strategies based on understanding the pathogenesis of the disease. This review attempts to highlight some of the recent advances in the understanding of the disease with a focus on molecular diagnostics. Genet Med 2010:12(3):145-152.