Spinal muscular atrophy diagnostics

Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (SMN), which exists in 2 nearly identical copies (SMN1 and SMN2). Exon 7 of SMN1 is homozygously absent in about 95% of spinal muscular atrophy patients, whereas the loss of SMN2 does not cause spinal muscular atrophy. Small mutations are found in the other 5% of affected patients, and these mutations cluster in the 3' end of SMN1, a region important for protein oligomerization. SMN1 dosage testing can be used to determine the SMN1 copy number and to detect spinal muscular atrophy carriers and affected compound heterozygotes. Dosage testing is compromised by the presence of 2 SMN1 copies per chromosome, which occurs in about 2% of carriers. Finally, although SMN2 produces less full-length transcript than SMN1, the number of SMN2 copies modulates the phenotype.