title: A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients.
abstract: Spinal muscular atrophy (SMA) is a frequent autosomal recessive disease characterized by degeneration of the motor neurons of the spinal cord causing proximal paralysis with muscle atrophy. The region on chromosome 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. We 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 in four unrelated patients. This deletion, which results in a frameshift and a premature stop codon, occurs on the same haplotype background, suggesting that a single mutational event is involved in the four families. The other patients showed either deletions of the SMN gene (49/54) or a gene conversion event changing SMN exon 7 into its highly homologous copy (cBCD541, 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.
authors.affiliation: Molecular Genetics Unit, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Bussaglia
authors.forename: O
authors.initials: O
authors.lastname: Clermont
authors.forename: E
authors.initials: E
authors.lastname: Tizzano
authors.forename: S
authors.initials: S
authors.lastname: Lefebvre
authors.forename: L
authors.initials: L
authors.lastname: Bürglen
authors.forename: C
authors.initials: C
authors.lastname: Cruaud
authors.forename: J A
authors.initials: JA
authors.lastname: Urtizberea
authors.forename: J
authors.initials: J
authors.lastname: Colomer
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: M
authors.initials: M
authors.lastname: Baiget
mesh_terms: D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein; D016368:Frameshift Mutation; D005785:Gene Conversion; D006801:Humans; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000145:classification / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D013030:Spain
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins