ArticleOrphanet journal of rare diseases2013
Functional and genetic characterization of the non-lysosomal glucosylceramidase 2 as a modifier for Gaucher disease.
Article in Orphanet journal of rare diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Refining Mouse Models of Gaucher Disease: Advancing Mechanistic Insights, Biomarker Discovery, and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Gaucher disease provides a unique window into Parkinson disease pathogenesis.Nature reviews. Neurology · 2024Review
- Lipid Dyshomeostasis and Inherited Cerebellar Ataxia.Molecular neurobiology · 2022Review
- Impact of Gba2 on neuronopathic Gaucher's disease and α-synuclein accumulation in medaka (Oryzias latipes).Molecular brain · 2021Article
- Histomorphometric analysis of liver biopsies of treated patients with Gaucher disease type 1.Autopsy & case reports · 2021Article
- Structure, metabolism and biological functions of steryl glycosides in mammals.The Biochemical journal · 2020Review
- Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson's disease.Molecular neurodegeneration · 2019Article
- Species-specific differences in nonlysosomal glucosylceramidase GBA2 function underlie locomotor dysfunction arising from loss-of-function mutations.The Journal of biological chemistry · 2019Article
- Exploring genetic modifiers of Gaucher disease: The next horizon.Human mutation · 2018Review
- Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease.Blood cells, molecules & diseases · 2018Article
- Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals.Journal of lipid research · 2017Article
- Lipids regulate the hydrolysis of membrane bound glucosylceramide by lysosomal β-glucocerebrosidase.Journal of lipid research · 2017Article
- Current and Novel Aspects on the Non-lysosomal β-Glucosylceramidase GBA2.Neurochemical research · 2016Review
- Accumulation of glucosylceramide in the absence of the beta-glucosidase GBA2 alters cytoskeletal dynamics.PLoS genetics · 2015Article
- Article
- The development and use of small molecule inhibitors of glycosphingolipid metabolism for lysosomal storage diseases.Journal of lipid research · 2014Review
- Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 12 institutions in 6 countries.
Funding
Abstract
backgroundGaucher disease (GD) is the most common inherited lysosomal storage disorder in humans, caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA1). GD is clinically heterogeneous and although the type of GBA1 mutation plays a role in determining the type of GD, it does not explain the clinical variability seen among patients. Cumulative evidence from recent studies suggests that GBA2 could play a role in the pathogenesis of GD and potentially interacts with GBA1.
methodsWe used a framework of functional and genetic approaches in order to further characterize a potential role of GBA2 in GD. Glucosylceramide (GlcCer) levels in spleen, liver and brain of GBA2-deficient mice and mRNA and protein expression of GBA2 in GBA1-deficient murine fibroblasts were analyzed. Furthermore we crossed GBA2-deficient mice with conditional Gba1 knockout mice in order to quantify the interaction between GBA1 and GBA2. Finally, a genetic approach was used to test whether genetic variation in GBA2 is associated with GD and/ or acts as a modifier in Gaucher patients. We tested 22 SNPs in the GBA2 and GBA1 genes in 98 type 1 and 60 type 2/3 Gaucher patients for single- and multi-marker association with GD.
resultsWe found a significant accumulation of GlcCer compared to wild-type controls in all three organs studied. In addition, a significant increase of Gba2-protein and Gba2-mRNA levels in GBA1-deficient murine fibroblasts was observed. GlcCer levels in the spleen from Gba1/Gba2 knockout mice were much higher than the sum of the single knockouts, indicating a cross-talk between the two glucosylceramidases and suggesting a partially compensation of the loss of one enzyme by the other. In the genetic approach, no significant association with severity of GD was found for SNPs at the GBA2 locus. However, in the multi-marker analyses a significant result was detected for p.L444P (GBA1) and rs4878628 (GBA2), using a model that does not take marginal effects into account.
conclusionsAll together our observations make GBA2 a likely candidate to be involved in GD etiology. Furthermore, they point to GBA2 as a plausible modifier for GBA1 in patients with GD.
Indexed as
Identifiers
What OpenQuestion holds
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.