IDENTIFICATION AND CHARACTERIZATION OF A SPINAL MUSCULAR ATROPHY-DETERMINING GENE

Spinal muscular atrophy (SMA) is a common fatal autosomal recessive di sorder characterized by degeneration of lower motor neurons, leading t o progressive paralysis with muscular atrophy. The gene for SMA has be en mapped to chromosome 5q13, where large-scale deletions have been re ported. We describe here the inverted duplication of a 500 kb element in normal chromosomes and narrow the critical region to 140 kb within the telomeric region. This interval contains a 20 kb gene encoding a n ovel protein of 294 amino acids. An highly homologous gene is present in the centromeric element of 95% of controls. The telomeric gene is e ither lacking or interrupted in 226 of 229 patients, and patients reta ining this gene (3 of 229) carry either a point mutation (Y272C) or sh ort deletions in the consensus splice sites of introns 6 and 7. These data suggest that this gene, termed the survival motor neuron (SMN) ge ne, is an SMA-determining gene.