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00925njm 22002777a 4500 dc Blasco Perez, Laura author Cuscó Martín, Ivon author Tizzano Ferrari, Eduardo Fidel author Costa Roger, Mar author 2022-05-02T12:15:27Z 2022-05-02T12:15:27Z 2021-08 Estructura híbrida; Atrofia muscular espinal; Neurona motora de supervivencia 1 Hybrid structure; Spinal muscular atrophy; Survival motor neuron 1 Estructura híbrida; Atròfia muscular espinal; Neurona motora de supervivència 1 After 26 years of discovery of the determinant survival motor neuron 1 and the modifier survival motor neuron 2 genes (SMN1 and SMN2, respectively), three SMN-dependent specific therapies are already approved by FDA and EMA and, as a consequence, worldwide SMA patients are currently under clinical investigation and treatment. Bi-allelic pathogenic variants (mostly deletions) in SMN1 should be detected in SMA patients to confirm the disease. Determination of SMN2 copy number has been historically employed to correlate with the phenotype, predict disease evolution, stratify patients for clinical trials and to define those eligible for treatment. In view that discordant genotype-phenotype correlations are present in SMA, besides technical issues with detection of SMN2 copy number, we have hypothesized that copy number determination is only the tip of the iceberg and that more deepen studies of variants, sequencing and structures of the SMN2 genes are necessary for a better understanding of the disease as well as to investigate possible influences in treatment responses. Here, we highlight the importance of a comprehensive approach of SMN1 and SMN2 genetics with the perspective to apply for better prediction of SMA in positive neonatal screening cases and early diagnosis to start treatments. This work was partially supported by Grants from Biogen and Roche (to E.F.T. supporting M.C.-R. and L.B.-P.), and from Spanish Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias and cofunded with ERDF funds (Grant No. FIS PI18/000687) (to E.F.T.). Atròfia muscular espinal - Tractament Neurones motores Farmacologia molecular DISEASES::Nervous System Diseases::Central Nervous System Diseases::Spinal Cord Diseases::Muscular Atrophy, Spinal Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Drug Therapy::Molecular Targeted Therapy ANATOMY::Nervous System::Neurons::Neurons, Efferent::Motor Neurons ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades de la médula espinal::atrofia muscular espinal Otros calificadores::Otros calificadores::/terapia ANATOMÍA::sistema nervioso::neuronas::neuronas eferentes::neuronas motoras TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::farmacoterapia::terapia molecular selectiva The Importance of Digging into the Genetics of SMN Genes in the Therapeutic Scenario of Spinal Muscular Atrophy