ArticleHuman genetics2008
Nonsense-mediated messenger RNA decay of survival motor neuron 1 causes spinal muscular atrophy.
Article in Human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Single NucleotideNeurology. Genetics · 2025Article
- Real-world evidence: Risdiplam in a patient with spinal muscular atrophy type I with a novel splicing mutation and one SMN2 copy.Human molecular genetics · 2024Article
- Genomic Variability in the Survival Motor Neuron Genes (International journal of molecular sciences · 2021Review
- Dual Mechanism of a New SMN1 Variant (c.835G>C, p.Gly279Arg) by Interrupting Exon 7 Skipping and YG Oligomerization in Causation of Spinal Muscular Atrophy.Journal of molecular neuroscience : MN · 2021Article
- Impact of missense mutations in survival motor neuron protein (SMN1) leading to Spinal Muscular Atrophy (SMA): A computational approach.Metabolic brain disease · 2018Article
- An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes.Scientific reports · 2018Article
- Different Stability and Proteasome-Mediated Degradation Rate of SMN Protein Isoforms.PloS one · 2015Article
- Molecular analysis, pathogenic mechanisms, and readthrough therapy on a large cohort of Kabuki syndrome patients.Human mutation · 2014Article
- Advances in therapeutic development for spinal muscular atrophy.Future medicinal chemistry · 2014Review
- Histone deacetylase inhibitors as potential treatment for spinal muscular atrophy.Genetics and molecular biology · 2013Review
- Genome-wide survey of interindividual differences of RNA stability in human lymphoblastoid cell lines.Scientific reports · 2013Article
- Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model.Human molecular genetics · 2012Article
- Subtle mutations in the SMN1 gene in Chinese patients with SMA: p.Arg288Met mutation causing SMN1 transcript exclusion of exon7.BMC medical genetics · 2012Article
- RNA processing pathways in amyotrophic lateral sclerosis.Neurogenetics · 2010Review
- Mutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene.Human genetics · 2009Article
- Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition.Human molecular genetics · 2009Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal recessive proximal spinal muscular atrophy (SMA) is a neurodegenerative disorder resulting from functional loss of survival motor neuron 1 (SMN1). Homozygous absence of SMN1 due to deletion or gene conversion accounts for about 96% of SMA cases. In the remaining 4%, subtle SMN1 mutations are commonly identified. Here, we describe two novel intragenic SMN1 mutations in three type I SMA individuals: a point mutation in exon 3 (c.469C > T) and a substitution in intron 4 (c.628-140A > G). In-vivo splicing assays demonstrated that the intronic substitution creates a novel splice donor site, culminating in aberrant splicing and insertion of 65 bp from intron 4 between exons 4 and 5 in SMN1 transcripts (c.627_628ins65). Both mutations render SMN1 transcripts susceptible to nonsense-mediated mRNA decay (NMD), resulting in mRNA degradation, insufficient SMN protein levels and development of an SMA phenotype. Treatment of patient cell lines with the translation inhibitors puromycin and emetine markedly increased the levels of mutant SMN1 transcripts. A similar effect was observed after siRNA-mediated knockdown of UPF1, a factor essential for NMD. This study provides first evidence that NMD of SMN1 transcripts is responsible for the molecular basis of disease in a subset of SMA patients.
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