title: Novel splice-site mutation in SMN1 associated with a very severe SMA-I phenotype.
abstract: Spinal muscular atrophy (SMA) is a genetic disorder characterized by degeneration of motor neurons and muscle weakness and atrophy. The majority of patients harbor homozygous SMN1 deletions, resulting in an SMN1-null genotype. A variable number of copies of SMN2, the centromeric copy of SMN1, fails to compensate for the absence of SMN1 but can act as a modifier. Less than 5% of patients with SMA display intragenic mutations on the second allele, detectable by direct sequencing. The effects of these mutations are not easily predictable, hindering a clear correlation with the clinical phenotype. We describe a novel SMN1 mutation that affected the donor splice site of exon 7 and resulted in an unusually severe SMA phenotype with rapid fatal outcome in an Italian infant.
authors.affiliation: Neurology Unit, Neuroscience Section, Department of Pathophysiology and Transplantation, Dino Ferrari Center, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Ronchi
authors.forename: Stefano Carlo
authors.initials: SC
authors.lastname: Previtali
authors.forename: Maria Grazia Natali
authors.initials: MG
authors.lastname: Sora
authors.forename: Graziano
authors.initials: G
authors.lastname: Barera
authors.forename: Benedetta
authors.initials: B
authors.lastname: Del Menico
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo Pietro
authors.initials: GP
authors.lastname: Comi
mesh_terms: D005091:Exons; D006801:Humans; D007223:Infant; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein