MISSENSE MUTATION CLUSTERING IN THE SURVIVAL MOTOR-NEURON GENE - A ROLE FOR A CONSERVED TYROSINE AND GLYCINE-RICH REGION OF THE PROTEIN IN RNA-METABOLISM

The Survival Motor Neuron (SMN) gene shows deletions in the majority o f patients with Spinal Muscular Atrophy (SMA), a disease of motor neur on degeneration. To date only two missense mutations have been reporte d in SMN in patients with SMA, The fact that no SMN-homologues have be en forthcoming from database searching has resulted in a lack of hypot heses concerning the structural and functional consequences of these m utations, Recently SMN has been shown to interact with heterogeneous n uclear ribonucleoproteins (hnRNPs) suggesting a role in mRNA metabolis m. We describe a novel missense mutation and the subsequent identifica tion of a triplicated tyrosine-glycine (Y-G) peptide sequence at the C -terminal of SMN which encompasses each of the three predicted amino a cid sequence substitutions. We have identified apparent orthologues of SMN in Caenorhabditis elegans and Schizosaccharomyces pombe. These se quences retain the highly conserved Y-G motif and provide additional s upport for a role of SMN in mRNA metabolism.