NAIP-deletion analysis in Malaysian patients with spinal muscular atrophy

Spinal Muscular Atrophy (SMA) is an autosomal recessive disease, which is characterized by degeneration of the anterior horn cells of the spinal cord. SMA is classified into 3 clinical subtypes, type I (severe), type II (intermediate), and type III (mild). Two genes, SMN1 and NAIP, have been identified as SMA-related genes. The SMN1 gene is now recognized as a responsible gene for the disease because it is deleted or mutated in most SMA patients. However, the role of the NAIP gene in SMA has not been fully clarified. To clarify the contribution of NAIP to the disease severity of SMA, we studied the relationship between NAIP-deletion and clinical phenotype in Malaysian patients. A total of 39 patients lacking SMN1 (12 type I, 19 type II, and 8 type III patients) were enrolled into this study. Seven out of 12 patients with type I SMA (approximately 60%) showed NAIP deletion. On the contrary, only 2 out of 20 type II patients and none of type III patients showed NAIP deletion. There was a statistically significant difference in NAIP-deletion frequency among the clinical subtypes (Fisher's exact probability test, p value = 0.014). In conclusion, according to our data that NAIP deletion was more frequent in type I SMA than in type II-III SMA, the NAIP gene may be a modifying factor for disease severity of SMA.