Quick MLPA test for quantification of SMN1 and SMN2 copy numbers.

Abstract Spinal muscular atrophy (SMA) is an autosomal recessive disease caused in about 95% of SMA patients by homozygous deletion of the survival motor neuron 1 ( SMN1 ) gene or its conversion to the highly homologous SMN2 gene. In the majority of cases, disease severity correlates inversely with increased SMN2 copy number. Because of the comparatively high incidence of healthy carriers and severity of the disease, detection of sequence alterations and quantification of SMN1 and SMN2 copy numbers are essential for exact diagnosis and genetic counselling. Several assays have been developed for this purpose. Multiplex ligation-dependent probe amplification (MLPA) is a versatile technique for relative quantification of different nucleic acid sequences in a single reaction. Here, we establish a quick MLPA-based assay for the detection of SMN1 and SMN2 copy numbers with high specificity and low complexity.