title: GBA2 Mutations Cause a Marinesco-Sjögren-Like Syndrome: Genetic and Biochemical Studies.
abstract: BACKGROUND
  With the advent new sequencing technologies, we now have the tools to understand the phenotypic diversity and the common occurrence of phenocopies. We used these techniques to investigate two Norwegian families with an autosomal recessive cerebellar ataxia with cataracts and mental retardation.
  
  
  RESULTS
  Single nucleotide polymorphism (SNP) chip analysis followed by Exome sequencing identified a 2 bp homozygous deletion in GBA2 in both families, c.1528_1529del [p.Met510Valfs*17]. Furthermore, we report the biochemical characterization of GBA2 in these patients. Our studies show that a reduced activity of GBA2 is sufficient to elevate the levels of glucosylceramide to similar levels as seen in Gaucher disease. Furthermore, leucocytes seem to be the proper enzyme source for in vitro analysis of GBA2 activity.
  
  
  CONCLUSIONS
  We report GBA2 mutations causing a Marinesco-Sjögren-like syndrome in two Norwegian families. One of the families was originally diagnosed with Marinesco-Sjögren syndrome based on an autosomal recessive cerebellar ataxia with cataracts and mental retardation. Our findings highlight the phenotypic variability associated with GBA2 mutations, and suggest that patients with Marinesco-Sjögren-like syndromes should be tested for mutations in this gene.
authors.affiliation: Department of Neurology, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Haugarvoll
authors.affiliation: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Stefan
authors.initials: S
authors.lastname: Johansson
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Rodriguez
authors.affiliation: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Helge
authors.initials: H
authors.lastname: Boman
authors.affiliation: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Bjørn Ivar
authors.initials: BI
authors.lastname: Haukanes
authors.affiliation: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Ove
authors.initials: O
authors.lastname: Bruland
authors.affiliation: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Francisco
authors.initials: F
authors.lastname: Roque
authors.affiliation: Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway.
authors.forename: Inge
authors.initials: I
authors.lastname: Jonassen
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Blomqvist
authors.affiliation: Department of Neurology, Førde Hospital, Førde, Norway.
authors.forename: Wenche
authors.initials: W
authors.lastname: Telstad
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Månsson
authors.affiliation: Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per Morten
authors.initials: PM
authors.lastname: Knappskog
authors.affiliation: Department of Neurology, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway.
authors.forename: Laurence A
authors.identifier: http://orcid.org/0000-0003-0988-276X
authors.initials: LA
authors.lastname: Bindoff
mesh_terms: D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D005962:Glucosylceramidase; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D013132:Spinocerebellar Degenerations / Q000235:genetics*; D001617:beta-Glucosidase / Q000235:genetics*
chemical_list: D001617:beta-Glucosidase; C517537:GBA2 protein, human; D005962:Glucosylceramidase