ArticleAmerican journal of human genetics2013
Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- Pooled it
- Hereditary Congenital Cataract With Spastic Paraplegia Associated With a Missense PAX6 Variant (p.Arg26Trp).Cureus · 2026Article
- Hypogonadotrophic hypogonadism in GBA2 associated spastic paraplegia type 46 (SPG46): a phenotypic expansion.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Review
- A multi-omics Mendelian randomization study identifies new therapeutic targets for alcohol use disorder and problem drinking.Nature human behaviour · 2025Article
- Hereditary spastic paraparesis type 46 (SPG46): new GBA2 variants in a large Italian case series and review of the literature.Neurogenetics · 2024Review
- Diving deep: zebrafish models in motor neuron degeneration research.Frontiers in neuroscience · 2024Review
- White matter abnormalities in 15 subjects with SPG76.Journal of neurology · 2023Article
- Gangliosides and Cell Surface Ganglioside Metabolic Enzymes in the Nervous System.Advances in neurobiology · 2023Article
- Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine.Translational neurodegeneration · 2022Review
- SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction.Human molecular genetics · 2022Article
- The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment.International journal of molecular sciences · 2022Review
- Lipid Dyshomeostasis and Inherited Cerebellar Ataxia.Molecular neurobiology · 2022Review
- A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans.Orphanet journal of rare diseases · 2022Review
- Development of a high-throughput tailored imaging method in zebrafish to understand and treat neuromuscular diseases.Frontiers in molecular neuroscience · 2022Article
- Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement.Frontiers in neurology · 2022Article
- Membrane lipid raft homeostasis is directly linked to neurodegeneration.Essays in biochemistry · 2021Review
- Mapping Sphingolipid Metabolism Pathways during Phagosomal Maturation.ACS chemical biology · 2021Article
- Spastic paraplegia type 46: novel and recurrent GBA2 gene variants in a compound heterozygous Italian patient with spastic ataxia phenotype.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
- Impact of Gba2 on neuronopathic Gaucher's disease and α-synuclein accumulation in medaka (Oryzias latipes).Molecular brain · 2021Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 12 institutions in 6 countries.
Funding
Abstract
Spastic paraplegia 46 refers to a locus mapped to chromosome 9 that accounts for a complicated autosomal-recessive form of hereditary spastic paraplegia (HSP). With next-generation sequencing in three independent families, we identified four different mutations in GBA2 (three truncating variants and one missense variant), which were found to cosegregate with the disease and were absent in controls. GBA2 encodes a microsomal nonlysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide and the hydrolysis of bile acid 3-O-glucosides. The missense variant was also found at the homozygous state in a simplex subject in whom no residual glucocerebrosidase activity of GBA2 could be evidenced in blood cells, opening the way to a possible measurement of this enzyme activity in clinical practice. The overall phenotype was a complex HSP with mental impairment, cataract, and hypogonadism in males associated with various degrees of corpus callosum and cerebellar atrophy on brain imaging. Antisense morpholino oligonucleotides targeting the zebrafish GBA2 orthologous gene led to abnormal motor behavior and axonal shortening/branching of motoneurons that were rescued by the human wild-type mRNA but not by applying the same mRNA containing the missense mutation. This study highlights the role of ceramide metabolism in HSP pathology.
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