ArticleThe Journal of clinical investigation1999
Non-pseudogene-derived complex acid beta-glucosidase mutations causing mild type 1 and severe type 2 gaucher disease.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 52 citations in OpenAlex.
- Gba1 E326K renders motor and non-motor symptoms with pathological α-synuclein, tau and glial activation.Brain : a journal of neurology · 2024Article
- Article
- The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines.Human molecular genetics · 2023Article
- Review
- Genetic variations inFrontiers in neurology · 2022Review
- Glucocerebrosidase Gene Therapy Induces Alpha-Synuclein Clearance and Neuroprotection of Midbrain Dopaminergic Neurons in Mice and Macaques.International journal of molecular sciences · 2021Article
- A Large-Scale Full GBA1 Gene Screening in Parkinson's Disease in the Netherlands.Movement disorders : official journal of the Movement Disorder Society · 2020Article
- Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic Parkinson's Disease and Dementia with Lewy Bodies.Molecular neurobiology · 2019Article
- Mitochondrial dysfunction associated with glucocerebrosidase deficiency.Neurobiology of disease · 2016Review
- GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease.Movement disorders : official journal of the Movement Disorder Society · 2016Article
- No evidence for substrate accumulation in Parkinson brains with GBA mutations.Movement disorders : official journal of the Movement Disorder Society · 2015Article
- The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease.Movement disorders : official journal of the Movement Disorder Society · 2013Article
- Gaucher disease: when molecular testing and clinical presentation disagree -the novel c.1226A>G(p.N370S)--RecNcil allele.Journal of inherited metabolic disease · 2011Article
- A neutral variant involved in a complex CFTR allele contributes to a severe cystic fibrosis phenotype.Human genetics · 2005Article
- Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease.American journal of human genetics · 2000Article
- Type 2 Gaucher disease: the collodion baby phenotype revisited.Archives of disease in childhood. Fetal and neonatal edition · 2000Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Gaucher disease is an autosomal recessive inborn error of glycosphingolipid metabolism caused by the deficient activity of the lysosomal hydrolase, acid beta-glucosidase. Three phenotypically distinct subtypes result from different acid beta-glucosidase mutations encoding enzymes with absent or low activity. A severe neonatal type 2 variant who presented with collodion skin, ichthyosis, and a rapid neurodegenerative course had two novel acid beta-glucosidase alleles: a complex, maternally derived allele, E326K+L444P, and a paternally inherited nonsense mutation, E233X. Because the only other non-pseudogene-derived complex allele, D140H+E326K, also had the E326K lesion and was reported in a mild type 1 patient with a D140H+E326K/K157Q genotype, these complex alleles and their individual mutations were expressed and characterized. Because the E233X mutation expressed no activity and the K157Q allele had approximately 1% normal specific activity based on cross-reacting immunologic material (CRIM SA) in the baculovirus system, the residual activity in both patients was primarily from their complex alleles. In the type 1 patient, the D140H+E326K allele was neuroprotective, encoding an enzyme with a catalytic efficiency similar to that of the N370S enzyme. In contrast, the E326K+L444P allele did not have sufficient activity to protect against the neurologic manifestations and, in combination with the inactive E233X lesion, resulted in the severe neonatal type 2 variant. Thus, characterization of these novel genotypes with non-pseudogene-derived complex mutations provided the pathogenic basis for their diverse phenotypes.
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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.