ArticleNeurology2017
Sphingosine 1-phosphate lyase deficiency causes Charcot-Marie-Tooth neuropathy.
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Article in Neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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49citing papers in PubMed, 1 pooled it
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Sphingosine phosphate lyase insufficiency syndrome: a systematic review.World journal of pediatrics : WJP · 2023Pooled it
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Biallelic variants in COX18 cause a mitochondrial disorder primarily manifesting as peripheral neuropathy.Brain : a journal of neurology · 2026Article
- Exploring the biological functions of PCOS: identifying hub androgen-related genes through bioinformatics.Frontiers in medicine · 2026Article
- Review
- Review
- Sphingosine phosphate lyase insufficiency syndrome as a primary immunodeficiency state.Advances in biological regulation · 2024Review
- Factors influencing survival in sphingosine phosphate lyase insufficiency syndrome: a retrospective cross-sectional natural history study of 76 patients.Orphanet journal of rare diseases · 2024Article
- Alternative splicing expands the clinical spectrum of NDUFS6-related mitochondrial disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Article
- Prevalence estimate of sphingosine phosphate lyase insufficiency syndrome in worldwide and select populations.Genetics in medicine open · 2024Article
- Sphingosine 1-Phosphate Lyase in the Developing and Injured Nervous System: a Dichotomy?Molecular neurobiology · 2023Review
- Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration.International journal of molecular sciences · 2023Review
- The role of sphingosine-1-phosphate in the development and progression of Parkinson's disease.Frontiers in cellular neuroscience · 2023Review
- Familial Glucocorticoid Deficiency: the changing landscape of an eponymous syndrome.Frontiers in endocrinology · 2023Review
- Sphingolipids in neurodegenerative diseases.Frontiers in neuroscience · 2023Review
- Congenital adrenal calcifications as the first clinical indication of sphingosine lyase insufficiency syndrome: A case report and review of the literature.American journal of medical genetics. Part A · 2022Review
- A retrospective analysis of endocrine disease in sphingosine-1-phosphate lyase insufficiency: case series and literature review.Endocrine connections · 2022Review
- Sphingosine Phosphate Lyase Is Upregulated in Duchenne Muscular Dystrophy, and Its Inhibition Early in Life Attenuates Inflammation and Dystrophy in Mdx Mice.International journal of molecular sciences · 2022Article
- Analyzing Opposing Interactions Between Sphingosine 1-Phosphate Lyase and Influenza A Virus.DNA and cell biology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Derek AtkinsonFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Jelena Nikodinovic GlumacFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Bob AsselberghFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Biljana ErmanoskaFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
David BlocquelFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Regula SteinerFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Alejandro Estrada-CuzcanoFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Kristien PeetersFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Tinne OomsFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Els De VriendtFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Xiang-Lei YangFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Thorsten HornemannFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland.
Vedrana Milic RasicFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland. albena.jordanova@molgen.vib-ua.be vedrana.milic.npk@gmail.com.
Albena JordanovaFrom the Molecular Neurogenomics Group (D.A., B.E., A.E.-C., K.P., T.O., E.D.V., A.J.), VIB Department of Molecular Genetics (B.A.), University of Antwerp, Belgium; Clinic for Neurology and Psychiatry for Children and Youth (J.N.G), Belgrade, Serbia; Faculty of Medicine (V.M.R.), Clinic for Neurology and Psychiatry for Children and Youth, University of Belgrade, Serbia; Departments of Chemical Physiology and Cell and Molecular Biology (D.B., X.-L.Y.), The Scripps Research Institute, La Jolla, CA; and Institute of Clinical Chemistry (R.S., T.H.), University Hospital Zurich, University of Zurich, Switzerland. albena.jordanova@molgen.vib-ua.be vedrana.milic.npk@gmail.com.
University of Belgrade · RSScripps Research Institute · USUniversity Children's Hospital, Belgrade · RS
Funding
Elucidating pathological mechanism of DI-CMTCR01NS085092 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI YANG, XIANG-LEI · 2013 to 2017
$2.2MNINDS NIH HHS R01 NS085092
Abstract
objectiveTo identify the unknown genetic cause in a nuclear family with an axonal form of peripheral neuropathy and atypical disease course.
methodsDetailed neurologic, electrophysiologic, and neuropathologic examinations of the patients were performed. Whole exome sequencing of both affected individuals was done. The effect of the identified sequence variations was investigated at cDNA and protein level in patient-derived lymphoblasts. The plasma sphingoid base profile was analyzed. Functional consequences of neuron-specific downregulation of the gene were studied in Drosophila.
resultsBoth patients present an atypical form of axonal peripheral neuropathy, characterized by acute or subacute onset and episodes of recurrent mononeuropathy. We identified compound heterozygous mutations cosegregating with disease and absent in controls in the SGPL1 gene, encoding sphingosine 1-phosphate lyase (SPL). The p.Ser361* mutation triggers nonsense-mediated mRNA decay. The missense p.Ile184Thr mutation causes partial protein degradation. The plasma levels of sphingosine 1-phosphate and sphingosine/sphinganine ratio were increased in the patients. Neuron-specific downregulation of the Drosophila orthologue impaired the morphology of the neuromuscular junction and caused progressive degeneration of the chemosensory neurons innervating the wing margin bristles.
conclusionsWe suggest SPL deficiency as a cause of a distinct form of Charcot-Marie-Tooth disease in humans, thus extending the currently recognized clinical and genetic spectrum of inherited peripheral neuropathies. Our data emphasize the importance of sphingolipid metabolism for neuronal function.
Indexed as
Codon, NonsenseMutation, MissenseAdultAldehyde-LyasesAnimalsAnimals, Genetically ModifiedCells, CulturedCharcot-Marie-Tooth DiseaseCohort StudiesDrosophila melanogasterDrosophila ProteinsFemaleHumansLymphocytesLysophospholipidsMaleAldehyde-LyasesCodon, NonsenseDrosophila ProteinsLysophospholipidsSphingosinesphingosine 1-phosphatesphingosine 1-phosphate lyase (aldolase)Sply protein, Drosophila
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