Ask about this productRelated genes to: SMN1 Blocking Peptide
- Gene:
- SMN1 NIH gene
- Name:
- survival of motor neuron 1, telomeric
- Previous symbol:
- SMA@, SMA
- Synonyms:
- BCD541, SMNT, SMA1, SMA2, SMA3, GEMIN1, TDRD16A
- Chromosome:
- 5q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1996-12-12
- Date modifiied:
- 2019-04-23
Related products to: SMN1 Blocking Peptide
Related articles to: SMN1 Blocking Peptide
- Spinal muscular atrophy is a severe neuromuscular disorder in which early treatment significantly improves outcomes. Prenatal diagnosis, particularly in fetuses with two copies, presents unique challenges. We report a late-preterm infant diagnosed with homozygous deletion and two copies, whose older sibling developed motor deficits despite early postnatal treatment. Following multidisciplinary consultation, delivery was planned at 35+4 weeks to enable immediate therapy. The infant received oral risdiplam on day 2 of life, followed by intravenous onasemnogene abeparvovec on day 59. Neurofilament light-chain levels were normal at birth and remained low, except for a transient rise after gene therapy. Initial motor development was normal until 2 months, when hypotonia appeared, followed by recovery and normalization by 5 months. This case suggests that planned preterm delivery with rapid postnatal treatment may be a pragmatic alternative to therapy for high-risk spinal muscular atrophy, pending further longitudinal data. - Source: PubMed
Publication date: 2026/01/19
Dangouloff TamaraChantraine FrédéricHennuy NadègeRigo VincentTribolet SophieBrande Laura VandenServais Laurent - Administration of high doses of a recombinant adeno-associated virus vector expressing the SMN1 protein (AAV-SMN1) can cause severe acute liver injury and death in non-human primates (NHPs) and, in rare cases, in patients. This study aimed to elucidate the molecular mechanisms underlying AAV-SMN1-induced liver damage. Transcriptomic analysis was performed using RNA-sequencing data from the livers of NHPs and rats receiving escalating doses of AAV-SMN1 and sacrificed 4-5 days later. Profound, dose-dependent transcriptomic changes were observed in NHPs. At the toxic, highest doses, there was significant upregulation of genes involved in the DNA damage/p53 response, pro-apoptotic unfolded protein response (UPR), and innate immune response, along with downregulation of genes associated with hepatocyte metabolic pathways. In contrast, NHPs receiving low doses and rats showed transcriptional changes indicative of antiviral pathway activation and T cell responses. In high-dose NHPs, SMN1 transgene levels correlated positively with pro-apoptotic UPR genes and inversely with hepatocyte identity genes. Here, we propose that AAV-induced hepatotoxicity involves cell-intrinsic mechanisms, such as UPR activation and the DNA damage/p53 response, which, along with the activation of innate immune responses, contribute to hepatocyte death. Targeting these pathways may offer a promising strategy for safer AAV-based therapies. - Source: PubMed
Publication date: 2026/01/30
Moeini PedramBilbao-Arribas MartínGuruceaga ElizabethTorrens-Baile JulenLanz Thomas AWhiteley Laurence OAragón TomasUnzu CarmenGonzález-Aseguinolaza Gloria - To investigate the genetic epidemiological characteristics of spinal muscular atrophy (SMA) among newborns in Foshan, and to evaluate the efficacy and clinical value of early disease-modifying therapy for affected infants. A retrospective cohort study was conducted on 132 850 newborns who underwent SMA genetic screening at the Department of Foshan Newborn Disease Screening Center, Foshan Women and children Hospital from June 2020 to October 2025. Clinical data were collected of the 132 850 newborns, as well and 5 confirmed SMA patients, including general characteristics, validation results via multiplex ligation-dependent probe amplification (MLPA), disease-modifying treatments, and motor function assessments. The carrier rate of survival motor neuron 1 (SMN1) gene exon 7 deletion and the incidence of SMA in Foshan were determined. Changes in muscle strength and motor milestones of confirmed SMA patients before and after early disease-modifying therapy were analyzed. Of the screened newborns, 2 378 cases were identified with heterozygous deletion of SMN1 exon 7, and 5 cases with homozygous deletion of SMN1 exon 7 (confirmed as SMA patients via MLPA). The carrier rate of SMN1 exon 7 deletion in Foshan newborns was 1/56 (2 383/132 850), and the SMA incidence (homozygous deletion of SMN1 exon 7) was 1/26 570 (5/132 850). Among the 5 diagnosed patients, 4 had 2 copies of SMN2 exon 7. One patient did not receive disease-modifying therapy and died at 2 months of age, while 3 other patients all received disease-modifying therapy before 1.5 months of age. After treatment, their muscle strength improved, and they achieved the motor milestones of walking with assistance, sitting with support, and standing with support. Among the 5 confirmed patients, case 5 had 3 copies of SMN2 exon 7 and received disease-modifying therapy at 1.1 months of age. No obvious muscle strength abnormality was observed before or after treatment, and this patient achieved independent walking at 13 months of age. The carrier rate of SMN1 gene exon 7 deletion among newborns in Foshan is low, and the incidence of SMA (homozygous deletion type of SMN1) is also low. Early newborn screening for SMA, along with early diagnosis and treatment, can effectively improve the motor function in affected infants. - Source: PubMed
Publication date: 2026/05/15
Yuan W XHuang XShao Q YWang J YChen W FSu X - Spinal muscular atrophy (SMA) is a neuromuscular disorder primarily caused by homozygous deletion of the SMN1 gene, with disease severity influenced by SMN2 copy number. Detecting SMN1 deletions is complicated by high sequence homology with SMN2 and complex genomic architecture. Here we applied long-read whole-genome sequencing (LR-WGS), multiplex ligation-dependent probe amplification (MLPA), and targeted PCR to two adult patients with type IV SMA. We identified and precisely mapped two novel large deletions encompassing the entire SMN1 locus and observed significantly reduced full-length SMN mRNA levels. Our findings demonstrate LR-WGS's capability to resolve complex structural variants in highly homologous regions. Integrating LR-WGS with orthogonal validation enhances diagnostic precision, informing genetic counseling and advancing molecular diagnostics for SMA. - Source: PubMed
Publication date: 2026/05/12
Zhong ZeyanMai JieniChen DinaLamu YangzongZhou WenjuanMao RuiZeng XiaoxuanZhang ZiyunDeng JunyuWu XuanweiChen JianhongLi Liang - Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in the survival motor neuron 1 gene (SMN1), yet significant phenotypic variability exists even among individuals sharing identical genetic backgrounds, including siblings, suggesting that factors beyond SMN2 copy number contribute substantially to clinical heterogeneity. Emerging evidence implicates environmental exposures and epigenetic mechanisms as key modulators of this variability. Hypoxia accelerates disease progression by promoting SMN2 exon 7 skipping through upregulation of the splicing repressors hnRNP A1 and Sam68, while metabolic dysfunctions including hepatic steatosis and dyslipidemia, independent of motor neuron degeneration, have been reported in approximately one third of SMA patients at autopsy. Differential DNA methylation at CpG sites upstream of the SMN2 promoter correlates with disease severity, identifying a potential epigenetic prognostic biomarker. The three currently approved disease-modifying therapies, nusinersen, risdiplam, and onasemnogene abeparvovec, have fundamentally transformed SMA management, yet their efficacy may be modulated by environmental factors including nutritional status, respiratory function, infection burden, and pre-existing immunity to viral vectors, underscoring the need for integrated environmental and epigenetic assessment in SMA clinical care and research. This review integrates SMA-specific evidence with mechanistically plausible hypotheses drawn from related neurodegenerative conditions, clearly distinguishing established findings from emerging concepts. We propose that integrating environmental monitoring, nutritional optimization, and epigenetic modulation with genetic therapies may enable precision medicine approaches that maximize therapeutic benefit across the SMA clinical spectrum. - Source: PubMed
Publication date: 2026/05/07
Gopi SanjayPrethiba SChandhru MKarthick Raja Namasivayam SArockiaraj Jesu