Home > Publications Database > Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia. > print

001     136803
005     20240321220134.0
024 7 _ |a 10.1016/j.ajhg.2012.11.021
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024 7 _ |a pmid:23332916
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024 7 _ |a pmc:PMC3567271
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024 7 _ |a 0002-9297
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024 7 _ |a 1537-6605
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024 7 _ |a altmetric:1182337
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037 _ _ |a DZNE-2020-03125
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Martin, Elodie
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245 _ _ |a Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia.
260 _ _ |a New York, NY
|c 2013
|b Elsevier
264 _ 1 |3 print
|2 Crossref
|b Elsevier BV
|c 2013-02-01
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 345 - Population Studies and Genetics (POF3-345)
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542 _ _ |i 2013-02-01
|2 Crossref
|u https://www.elsevier.com/tdm/userlicense/1.0/
542 _ _ |i 2013-09-16
|2 Crossref
|u https://www.elsevier.com/open-access/userlicense/1.0/
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Zebrafish Proteins
|2 NLM Chemicals
650 _ 7 |a beta-Glucosidase
|0 EC 3.2.1.21
|2 NLM Chemicals
650 _ 7 |a GBA2 protein, human
|0 EC 3.2.1.45
|2 NLM Chemicals
650 _ 7 |a GBA2 protein, zebrafish
|0 EC 3.2.1.45
|2 NLM Chemicals
650 _ 2 |a Adolescent
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Child
|2 MeSH
650 _ 2 |a Child, Preschool
|2 MeSH
650 _ 2 |a Family
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Infant
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Motor Neurons: pathology
|2 MeSH
650 _ 2 |a Mutation: genetics
|2 MeSH
650 _ 2 |a Neuroimaging
|2 MeSH
650 _ 2 |a Pedigree
|2 MeSH
650 _ 2 |a Spastic Paraplegia, Hereditary: enzymology
|2 MeSH
650 _ 2 |a Spastic Paraplegia, Hereditary: genetics
|2 MeSH
650 _ 2 |a Young Adult
|2 MeSH
650 _ 2 |a Zebrafish
|2 MeSH
650 _ 2 |a Zebrafish Proteins: genetics
|2 MeSH
650 _ 2 |a beta-Glucosidase: genetics
|2 MeSH
700 1 _ |a Schüle, Rebecca
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700 1 _ |a Smets, Katrien
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700 1 _ |a Rastetter, Agnès
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700 1 _ |a Boukhris, Amir
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700 1 _ |a Loureiro, José L
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700 1 _ |a Gonzalez, Michael A
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700 1 _ |a Mundwiller, Emeline
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700 1 _ |a Deconinck, Tine
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700 1 _ |a Wessner, Marc
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700 1 _ |a Jornea, Ludmila
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700 1 _ |a Oteyza, Andrés Caballero
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700 1 _ |a Durr, Alexandra
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700 1 _ |a Martin, Jean-Jacques
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700 1 _ |a Schöls, Ludger
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700 1 _ |a Mhiri, Chokri
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700 1 _ |a Lamari, Foudil
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700 1 _ |a Züchner, Stephan
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700 1 _ |a De Jonghe, Peter
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700 1 _ |a Kabashi, Edor
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700 1 _ |a Brice, Alexis
|0 P:(DE-HGF)0
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|e Corresponding author
700 1 _ |a Stevanin, Giovanni
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773 1 8 |a 10.1016/j.ajhg.2012.11.021
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|t The American Journal of Human Genetics
|v 92
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773 _ _ |a 10.1016/j.ajhg.2012.11.021
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