title: A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11β gene.
abstract: BACKGROUND
  Peroxisomes are organelles that proliferate continuously and play an indispensable role in human metabolism. Consequently, peroxisomal gene defects can cause multiple, often severe disorders, including the peroxisome biogenesis disorders. Currently, 13 different PEX proteins have been implicated in various stages of peroxisome assembly and protein import. Defects in any of these proteins result in a peroxisome biogenesis disorder. The authors present here a novel genetic defect specifically affecting the division of peroxisomes.
  
  
  METHODS
  The authors have studied biochemical and microscopical peroxisomal parameters in cultured patient fibroblasts, sequenced candidate PEX genes and determined the consequence of the identified PEX11β gene defect on peroxisome biogenesis in patient fibroblasts at different temperatures.
  
  
  RESULTS
  The patient presented with congenital cataracts, mild intellectual disability, progressive hearing loss, sensory nerve involvement, gastrointestinal problems and recurrent migraine-like episodes. Although microscopical investigations of patient fibroblasts indicated a clear defect in peroxisome division, all biochemical parameters commonly used for diagnosing peroxisomal disorders were normal. After excluding mutations in all PEX genes previously implicated in peroxisome biogenesis disorders, it was found that the defect was caused by a homozygous non-sense mutation in the PEX11β gene. The peroxisome division defect was exacerbated when the patient's fibroblasts were cultured at 40°C, which correlated with a marked decrease in the expression of PEX11γ.
  
  
  CONCLUSIONS
  This novel isolated defect in peroxisome division expands the clinical and genetic spectrum of peroxisomal disorders and indicates that peroxisomal defects exist, which cannot be diagnosed by standard laboratory investigations.
authors.affiliation: Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Merel S
authors.initials: MS
authors.lastname: Ebberink
authors.forename: Janet
authors.initials: J
authors.lastname: Koster
authors.forename: Gepke
authors.initials: G
authors.lastname: Visser
authors.forename: Francjan van
authors.initials: Fv
authors.lastname: Spronsen
authors.forename: Irene
authors.initials: I
authors.lastname: Stolte-Dijkstra
authors.forename: G Peter A
authors.initials: GP
authors.lastname: Smit
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Fock
authors.forename: Stephan
authors.initials: S
authors.lastname: Kemp
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Hans R
authors.initials: HR
authors.lastname: Waterham
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D018901:Peroxisomal Disorders / Q000235:genetics*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013696:Temperature; D014162:Transfection
chemical_list: D008565:Membrane Proteins; C490453:PEX11B protein, human; C486770:PEX11G protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins