title: [Molecular basis of spinal muscular atrophy: th SMN gene].
abstract: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration and loss of motor neurons of the anterior horn of the spinal cord. The clinical manifestations include proximal symmetric weakness and progressive atrophy of muscle. SMA is classified by age of onset, severity of symptoms, and evolution in three groups: type I, severe or Werdnig-Hoffmann disease, type II or intermediate and type III, moderate-mild, Kugelberg-Welander disease. The identification of the SMN1 gene as determinant of SMA opened new alternatives to study the disease. Most of the patients have deletions and conversion of SMN1 and in a small number of cases, point mutations were detected. There is no obvious genotype-phenotype correlation because homozygous absence of SMN1 was associated to a wide spectrum of manifestations from congenital disease to non symptomatic cases. Modifier factors, such as the number of copies of SMN2, could influence the phenotype. Other possible modifier genes are under study. The SMN gene is expressed in various neuronal populations. However, only motor neurons are responsible for the manifestations of the disease. The SMN protein is part of a complex with various proteins involved in the splicing reaction. This apparent essential function for all cells could be critical in motor neurons. When SMN1 is absent or dysfunctional, the motor neurons could be more sensitive because they have an increased transcription activity. In this situation, other cells and tissues could be protected by genetic or cellular factors still undiscovered.
authors.affiliation: Servicio de Genética, Hospital de la Santa Creu i Sant Pau, Barcelona. etizzano@hsp.santpau.es
authors.forename: E
authors.initials: E
authors.lastname: Tizzano
authors.forename: M
authors.initials: M
authors.lastname: Baiget
mesh_terms: D000483:Alleles; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D051616:Neuronal Apoptosis-Inhibitory Protein; D010641:Phenotype; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C496800:NAIP protein, human; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
vernacular_title: Bases moleculares de la atrofia muscular espinal: el gen SMN.