ArticleAmerican journal of human genetics2012
Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 152 citations in OpenAlex.
- Fluorogenic Tissue-Based Assessment of Acid Ceramidase Activity.Bio-protocol · 2026Article
- Multisystem Complications in Spinal Muscular Atrophy Type III: Chronic Respiratory Failure and Intractable Epilepsy.Cureus · 2026Article
- Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development.Journal of neurochemistry · 2025Review
- A novel intronic variant in the ASAH1 gene enhances aberrant splicing, causing spinal muscular atrophy with progressive myoclonic epilepsy.Italian journal of pediatrics · 2025Article
- Acid Ceramidase Deficiency: New Insights on SMA-PME Natural History, Biomarkers, andNeurology. Genetics · 2025Article
- The analgesic effect of green light on neuropathic pain: a mini-review of the literature and a proposal for future work.Frontiers in pain research (Lausanne, Switzerland) · 2025Review
- ASAH1 Variants Causing Spinal Muscular Atrophy Phenotype.Indian journal of pediatrics · 2024Article
- Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity.Communications biology · 2024Article
- Targeting acid ceramidase enhances antitumor immune response in colorectal cancer.Journal of advanced research · 2024Article
- Review
- Clinical and Genetic Profiles of 5q- and Non-5q-Spinal Muscular Atrophy Diseases in Pediatric Patients.Genes · 2024Review
- Adiponectin overexpression improves metabolic abnormalities caused by acid ceramidase deficiency but does not prolong lifespan in a mouse model of Farber Disease.Molecular genetics and metabolism reports · 2024Article
- Genetic characterization of non-5q proximal spinal muscular atrophy in a French cohort: the place of whole exome sequencing.European journal of human genetics : EJHG · 2024Article
- Identification of a NovelIranian journal of child neurology · 2024Article
- Acid ceramidase regulates innate immune memory.Cell reports · 2023Article
- BiallelicJournal of medical genetics · 2023Article
- Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum.Italian journal of pediatrics · 2023Article
- Spinal muscular atrophy-like phenotype in a mouse model of acid ceramidase deficiency.Communications biology · 2023Article
- Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration.International journal of molecular sciences · 2023Review
- Zebra-Sphinx: Modeling Sphingolipidoses in Zebrafish.International journal of molecular sciences · 2023Review
12 more citing papers are in PubMed but not listed here.
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17 authors at 6 institutions in 4 countries.
Funding
Abstract
Spinal muscular atrophy (SMA) is a clinically and genetically heterogeneous disease characterized by the degeneration of lower motor neurons. The most frequent form is linked to mutations in SMN1. Childhood SMA associated with progressive myoclonic epilepsy (SMA-PME) has been reported as a rare autosomal-recessive condition unlinked to mutations in SMN1. Through linkage analysis, homozygosity mapping, and exome sequencing in three unrelated SMA-PME-affected families, we identified a homozygous missense mutation (c.125C>T [p.Thr42Met]) in exon 2 of ASAH1 in the affected children of two families and the same mutation associated with a deletion of the whole gene in the third family. Expression studies of the c.125C>T mutant cDNA in Farber fibroblasts showed that acid-ceramidase activity was only 32% of that generated by normal cDNA. This reduced activity was able to normalize the ceramide level in Farber cells, raising the question of the pathogenic mechanism underlying the CNS involvement in deficient cells. Morpholino knockdown of the ASAH1 ortholog in zebrafish led to a marked loss of motor-neuron axonal branching, a loss that is associated with increased apoptosis in the spinal cord. Our results reveal a wide phenotypic spectrum associated with ASAH1 mutations. An acid-ceramidase activity below 10% results in Farber disease, an early-onset disease starting with subcutaneous lipogranulomata, joint pain, and hoarseness of the voice, whereas a higher residual activity might be responsible for SMA-PME, a later-onset phenotype restricted to the CNS and starting with lower-motor-neuron disease.
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