ArticleAmerican journal of human genetics2010
Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I.
Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 186 citations in OpenAlex.
- Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Trial
- Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1.The Journal of clinical investigation · 2011Trial
- Mitochondrial energetic failure underlies FLVCR1-related sensory neuropathy.Communications biology · 2026Article
- Lipid ciliology: specialized ciliary membrane lipids in physiology and disease.Frontiers in cell and developmental biology · 2026Review
- Review
- Very long-chain fatty acids drive 1-deoxySphingolipid toxicity.Nature communications · 2025Article
- Don't Be Surprised When These Surprise You: Some Infrequently Studied Sphingoid Bases, Metabolites, and Factors That Should Be Kept in Mind During Sphingolipidomic Studies.International journal of molecular sciences · 2025Review
- Human genetic defects of sphingolipid synthesis.Journal of inherited metabolic disease · 2025Review
- Enzymes of sphingolipid metabolism as transducers of metabolic inputs.Biochemical Society transactions · 2024Review
- Functional and Molecular Characterization of NewGenes · 2024Article
- Sphingolipid biosynthesis is essential for metabolic rewiring during TScience advances · 2024Article
- SPTLC2 variants are associated with early-onset ALS and FTD due to aberrant sphingolipid synthesis.Annals of clinical and translational neurology · 2024Article
- Recurrent de novoJournal of neurology, neurosurgery, and psychiatry · 2024Article
- Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.Journal of neuromuscular diseases · 2024Review
- The Implication of Sphingolipids in Viral Infections.International journal of molecular sciences · 2023Review
- Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies.Brain : a journal of neurology · 2023Article
- Structure of the ceramide-bound SPOTS complex.Nature communications · 2023Article
- Enhanced insulin-regulated phagocytic activities support extreme health span and longevity in multiple populations.Aging cell · 2023Article
- SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia.Brain : a journal of neurology · 2023Article
- Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 9 institutions in 5 countries.
Funding
Abstract
Hereditary sensory and autonomic neuropathy type I (HSAN-I) is an axonal peripheral neuropathy associated with progressive distal sensory loss and severe ulcerations. Mutations in the first subunit of the enzyme serine palmitoyltransferase (SPT) have been associated with HSAN-I. The SPT enzyme catalyzes the first and rate-limiting step in the de novo sphingolipid synthesis pathway. However, different studies suggest the implication of other genes in the pathology of HSAN-I. Therefore, we screened the two other known subunits of SPT, SPTLC2 and SPTLC3, in a cohort of 78 HSAN patients. No mutations were found in SPTLC3, but we identified three heterozygous missense mutations in the SPTLC2 subunit of SPT in four families presenting with a typical HSAN-I phenotype. We demonstrate that these mutations result in a partial to complete loss of SPT activity in vitro and in vivo. Moreover, they cause the accumulation of the atypical and neurotoxic sphingoid metabolite 1-deoxy-sphinganine. Our findings extend the genetic heterogeneity in HSAN-I and enlarge the group of HSAN neuropathies associated with SPT defects. We further show that HSAN-I is consistently associated with an increased formation of the neurotoxic 1-deoxysphinganine, suggesting a common pathomechanism for HSAN-I.
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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.