ArticleAmerican journal of human genetics2009
A positive modifier of spinal muscular atrophy in the SMN2 gene.
Article in American journal of human genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
182 citing papers in PubMed, 310 citations in OpenAlex.
- Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial.Nature medicine · 2022Trial
- Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial.Nature medicine · 2022Trial
- Spinal muscular atrophy within Amish and Mennonite populations: Ancestral haplotypes and natural history.PloS one · 2018Trial
- SMA valiant trial: a prospective, double-blind, placebo-controlled trial of valproic acid in ambulatory adults with spinal muscular atrophy.Muscle & nerve · 2014Trial
- Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study.PloS one · 2012Trial
- Trial
- Proband-independent noninvasive prenatal diagnosis for spinal muscular atrophy: early detection paving the way for early prenatal treatment.Annals of medicine · 2026Article
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Clinical Characterization of Patients With 5q Spinal Muscular Atrophy Types 2 and 3 in Brazil: A Cross-Sectional Observational Study.Clinical genetics · 2026Observational
- Real-world 12-month outcomes of Risdiplam in spinal muscular atrophy types 2 and 3: A Brazilian cohort.Clinics (Sao Paulo, Brazil) · 2026Article
- Onasemnogene Abeparvovec in Patients With SMA: Interim Results of the RESTORE Registry in Japan.Annals of clinical and translational neurology · 2026Article
- Cis- and Trans-Regulatory Factors Independently Shape Phenotypic Heterogeneity of Retinitis Pigmentosa.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multimodal characterisation of the SMN locus in SMA: copy number quantification and hybrid gene identification.NPJ genomic medicine · 2026Article
- Nusinersen for type-III spinal muscular atrophy: a 12-month retrospective study in a Brazilian cohort.Arquivos de neuro-psiquiatria · 2026Article
- First combined analysis ofMolecular genetics and metabolism reports · 2026Article
- Early life safety profiling of gene therapy for spinal muscular atrophy.Gene therapy · 2026Article
- Single NucleotideNeurology. Genetics · 2025Article
- In utero therapy for spinal muscular atrophy: closer to clinical translation.Brain : a journal of neurology · 2025Review
- Advancing personalized spinal muscular atrophy care: matching the right biomarker to the right patient at the right time.Journal of neurology · 2025Review
- Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.International journal of molecular sciences · 2025Review
122 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is a common autosomal-recessive motor neuron disease caused by the homozygous loss of the SMN1 gene. A nearly identical gene, SMN2, has been shown to decrease the severity of SMA in a dose-dependent manner. However SMN2 is not the sole phenotypic modifier, because there are discrepant SMA cases in which the SMN2 copy number does not explain the clinical phenotype. This report describes three unrelated SMA patients who possessed SMN2 copy numbers that did not correlate with the observed mild clinical phenotypes. A single base substitution in SMN2, c.859G>C,, was identified in exon 7 in the patients' DNA. We now show that the change creates a new exonic splicing enhancer element and increases the amount of full-length transcripts, thus resulting in the less severe phenotypes. This demonstrates that the c.859G>C substitution is a positive modifier of the SMA phenotype and that not all SMN2 genes are equivalent. We have shown not only that the SMA phenotype is modified by the number of SMN2 genes but that SMN2 sequence variations can also affect the disease severity.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.