A FRAME-SHIFT DELETION IN THE SURVIVAL MOTOR-NEURON GENE IN SPANISH SPINAL MUSCULAR-ATROPHY PATIENTS

Spinal muscular atrophy (SMA) is a frequent autosomal recessive diseas e characterized by degeneration of the motor neurons of the spinal cor d causing proximal paralysis with muscle atrophy(1,2). The region on c hromosome 5q13 encompassing the disease gene is particularly unstable and prone to large-scale deletions whose characterization recently led to the identification of the survival motor neuron (SMN) gene(3,4). W e now present a genetic analysis of 54 unrelated Spanish SMA families that has revealed a 4-basepair (bp) deletion (AGAG) in exon 3 of SMN i n four unrelated patients. This deletion, which results in a frameshif t and a premature stop codon, occurs on the same haplotype background, suggesting that a single mutational event is involved in the four fam ilies. The other patients showed either deletions of the SMN gene (49/ 54) or a gene conversion event changing SMN exon 7 into its highly hom ologous copy ((C)BCD541, 1/54). This observation gives strong support to the view that mutations of the SMN gene are responsible for the SMA phenotype as it is the first frameshift mutation reported in SMA.