ArticleThe Journal of clinical investigation2017
Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 94 papers, 1 of them a synthesis that pooled it.
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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.
Sphingosine Phosphate Lyase Insufficiency Syndrome - Observational Study and Patient Registry (International)
Natural History and Phenotypic Spectrum of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)
Who cites it
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.
- Sphingosine phosphate lyase insufficiency syndrome: a systematic review.World journal of pediatrics : WJP · 2023Pooled it
- Review
- Exploring the biological functions of PCOS: identifying hub androgen-related genes through bioinformatics.Frontiers in medicine · 2026Article
- Hypoxia-inducible factor 2α overexpression in podocytes ameliorates lipid metabolism disorders in diabetic kidney disease by inhibiting S1P.Renal failure · 2025Article
- The enzyme SMPDL3b in podocytes decouples proteinuria from chronic kidney disease progression in experimental Alport Syndrome.Kidney international · 2025Article
- Adrenal insufficiency in inborn errors of metabolism and vice versa: Case reports and review of the literature.Molecular genetics and metabolism reports · 2025Review
- Mechanisms of podocyte injury in genetic kidney disease.Pediatric nephrology (Berlin, Germany) · 2025Review
- Sphingolipid signaling in kidney diseases.American journal of physiology. Renal physiology · 2025Review
- Review
- Clinical presentation and management challenges of sphingosine-1-phosphate lyase insufficiency syndrome associated with an SGPL1 variant: a case report.BMC pediatrics · 2025Article
- Lipid metabolism in the adrenal gland.Frontiers in endocrinology · 2025Review
- 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
- Prevalence estimate of sphingosine phosphate lyase insufficiency syndrome in worldwide and select populations.Genetics in medicine open · 2024Article
- Kidney derived apolipoprotein M and its role in acute kidney injury.Frontiers in pharmacology · 2024Article
- Sphingosine 1-Phosphate Lyase in the Developing and Injured Nervous System: a Dichotomy?Molecular neurobiology · 2023Review
- AAV-SPL 2.0, a Modified Adeno-Associated Virus Gene Therapy Agent for the Treatment of Sphingosine Phosphate Lyase Insufficiency Syndrome.International journal of molecular sciences · 2023Article
- Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease.Nature reviews. Nephrology · 2023Review
- Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation.Cell metabolism · 2023Article
- Identification of Glomerular and Plasma Apolipoprotein M as Novel Biomarkers in Glomerular Disease.Kidney international reports · 2023Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 9 institutions in 8 countries.
Funding
Abstract
Primary adrenal insufficiency is life threatening and can present alone or in combination with other comorbidities. Here, we have described a primary adrenal insufficiency syndrome and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1). SGPL1 executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P). Mutations in other upstream components of the pathway lead to harmful accumulation of lysosomal sphingolipid species, which are associated with a series of conditions known as the sphingolipidoses. In this work, we have identified 4 different homozygous mutations, c.665G>A (p.R222Q), c.1633_1635delTTC (p.F545del), c.261+1G>A (p.S65Rfs*6), and c.7dupA (p.S3Kfs*11), in 5 families with the condition. In total, 8 patients were investigated, some of whom also manifested other features, including ichthyosis, primary hypothyroidism, neurological symptoms, and cryptorchidism. Sgpl1-/- mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology. Sgpl1-/- mice displayed disrupted adrenocortical zonation and defective expression of steroidogenic enzymes as well as renal histology in keeping with a glomerular phenotype. In summary, we have identified SGPL1 mutations in humans that perhaps represent a distinct multisystemic disorder of sphingolipid metabolism.
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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.