Current Aspects in the Molecular Genetics and Diagnostics of Spinal Muscular Atrophy

Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations of the SMN1 gene on 5q13. It leads to progressive muscle wasting and paralysis as a result of degeneration of anterior horn cells of the spinal cord. The most frequent mutation is biallelic deletion of exon 7 of the SMN1 gene. About 5-6% of SMA patients present compound heterozygosity with a point mutation on one allele and deletion on the other; the remaining cases are likely to be related to non-5q-linked defects. Introduction of a quantitative polymerase chain reaction-based test further enhances the diagnostic potential by increasing the detection rate of cases with the biallelic exon 7 deletion in SMN1 and point mutations. Due to the higher prevalence of SMA than other autosomal recessive disorders and lack of efficient medical treatment, accurate identification of SMA carriers in general populations is much more important to reduce the social and financial burden of SMA.