Researchers used a DNA test called MLPA to look at seven people with suspected spinal muscular atrophy and found two different patterns of small deletions in the SMN1 gene. Both patterns always removed exon 7, which is the key piece that causes the disease, and these tiny deletions would have been missed by older testing methods.

To explore the diversity of mutations in survival motor neuron gene 1 (SMN1) by analyzing seven cases of partial deletion of SMN1 gene. Seven patients suspected spinal muscular atrophy (SMA) were recruited from 2011 to 2013. Multiplex ligation-dependent probe amplification (MLPA) for genetic testing of SMA was based on the commercially available SALSA MLPA kit P021-A2. Then the data were analyzed by the software Coffalyser.Negative control samples were chosen with two copies of SMN1 and SMN2. Positive control samples were chosen with zero copies of SMN1 and two copies of SMN2. According to the product description (www.mlpa.com): for exon 7 and 8 of SMN1 and SMN2: a ratio of <0.7 indicates 1 copy, a ratio of 0.7-1.3 2 copies, a ratio of 1.3-1.7 3 copies and a ratio of 1.7-2.3 4 copies. For exon 1, 4, 6, 8 of SMN gene (SMN1+SMN2): a ratio <0.4 indicates 1 copy, a ratio of 4.0-0.6 2 copies, a ratio of 0.7-0.9 3 copies and a ratio of 0.9-1.1 4 copies. All samples were analyzed in duplicate. Using MLPA for clinical diagnostics, two types of partial deletions of SMN1were identified in 7 patients.Since exon 8 is not translated and has no effect on the function of SMN protein, exons 1, 4, 6, 7 were targeted.One had an isolated deletion of exon 7 while the other ones were caused by the deletions of exon 1, 4 and 7. These mutations were not detected by conventional diagnostic methods. Both types of partial deletions of SMN1 gene contained a deletion of exon 7. Two types of partial deletions of SMN1 gene indicate that the structure of SMN gene is unstable leading to a variety of mutation forms. But the major cause of SMA lies in a deletion of exon 7 of SMN1 gene.