Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by progressive degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalized weakness. The clinical phenotype ranges from a severe infantile form with a limited life expectancy to an adult-onset mild form of the disease. In the majority of cases, the disease is caused by the homozygous absence of the survival motor neuron 1 (SMN1) gene.
The highly homologous survival motor neuron 2 (SMN2) gene differs from SMN1 by a single coding nucleotide resulting in a splicing defect and reduced SMN2 function. SMN2 copy number is a modifier of disease severity. Patients with a higher SMN2 copy number usually present with a milder clinical phenotype.
To address the clinical importance of accurate and efficient SMN1 and SMN2 copy number analysis, we developed a custom bioinformatic analysis based on next-generation sequencing (NGS) data combined with a novel RNase H2-dependent PCR (rhPCR) for confirmation analysis.
We established an accurate and high-throughput approach to test for SMN1 and SMN2 copy numbers in blood and saliva samples enabling diagnostics of SMA and application of novel therapeutic strategies.
Keywords: Spinal muscular atrophy (SMA), SMN1, SMN2, copy number variation (CNV), next-generation sequencing (NGS), RNase H-dependent PCR (rhPCR)
Authors: Seppälä EH, Saarinen I, Tallila J, Hathaway J, Tuupanen S, Turpeinen H, Kangas-Kontio T, Schleit J, Tommiska J, Salminen E, Salmenperä P, Sistonen J, Gentile M, Myllykangas S, Paananen J, Alastalo TP, Koskenvuo J