Molecular diagnosis of spinal muscular atrophy

Spinal muscular atrophy (SMA) is the second most common fatal disease of childhood with autosomal dominant mode of inheritance, and in its less severe form the third most common neuromuscular disease of childhood after Duchenne muscular dystrophy. The genetic defect was found to be on the long arm of chromosome 5 (5q11.2-q13.3) where many genes and microsatellite markers were missing. One of the most important genes is the Survival Motor Neuron (SMN) gene which is homozygously missing in 90% of SMA patients. Another important gene, the Neuronal Apoptosis Inhibitory Protein (NAIP) gene was found to be defective in 67% of SMA type I patients. Studies so far suggest SMA occurs when the genes on the long arm of chromosome 5 are mutated or deleted. Recently our hospital encountered 2 SMA patients of type I and II respectively. These patients both had homozygously defective SMN genes but intact NAIP genes. We are reporting these cases with bibliographic review and discussion. Korean SMA patients presumably have defects in SMN genes similar to those found in European patients, although the significance of NAIP genes remains to be established. SMN gene defects can be easily diagnosed using PCR and restriction enzymes, and this method could be applied towards convenient prenatal diagnosis and towards screening for family members at risk.