title: Identification of a novel PEX14 mutation in Zellweger syndrome.
abstract: BACKGROUND
  Peroxisome biogenesis disorders are a clinically and genetically heterogeneous group of very severe autosomal recessive disorders caused by impaired peroxisome biogenesis. The prototype of this group of disorders is the cerebro-hepato-renal syndrome of Zellweger.
  
  
  RESULTS
  Here we report a patient with Zellweger syndrome, who presented at the age of 3 months with icterus, dystrophy, axial hypotonia, facial dysmorphy, posterior embryotoxon, and hepatomegaly. Abnormal findings of metabolic screening tests included hyperbilirubinaemia, hypoketotic dicarboxylic aciduria, increased C(26:0) and decreased C(22:0) plasma levels, and strongly reduced plasmalogen concentrations. In fibroblasts, both peroxisomal alpha- and beta-oxidation were impaired. Liver histology revealed bile duct paucity, cholestasis, arterial hyperplasia, very small branches of the vena portae, and parenchymatic destruction. Immunocytochemical analysis of cultured fibroblasts demonstrated that the cells contain peroxisomal remnants lacking apparent matrix protein content and PEX14, a central membrane component of the peroxisomal matrix protein import machinery. Transfection of fibroblasts with a plasmid coding for wild-type PEX14 restored peroxisomal matrix protein import, indicating that the primary genetic defect affecting the patient is indeed linked to PEX14. Mutational analysis of this gene revealed a genomic deletion leading to the deletion of exon 3 from the coding DNA (c.85-?_170+?del) and a concomitant change of the reading frame (p.[Ile29_Lys56del;Gly57GlyfsX2]).
  
  
  CONCLUSIONS
  This report represents the second PEX14-deficiency associated with Zellweger syndrome and the first documentation of a PEX14-deficient patient with detailed clinical follow-up and biochemical, morphological, and radiological data.
authors.forename: S J
authors.initials: SJ
authors.lastname: Huybrechts
authors.forename: P P
authors.initials: PP
authors.lastname: Van Veldhoven
authors.forename: I
authors.initials: I
authors.lastname: Hoffman
authors.forename: R
authors.initials: R
authors.lastname: Zeevaert
authors.forename: R
authors.initials: R
authors.lastname: de Vos
authors.forename: P
authors.initials: P
authors.lastname: Demaerel
authors.forename: M
authors.initials: M
authors.lastname: Brams
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.forename: M
authors.initials: M
authors.lastname: Fransen
authors.forename: D
authors.initials: D
authors.lastname: Cassiman
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D021901:DNA, Intergenic; D005091:Exons / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D008099:Liver / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020675:Peroxisomes / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D015211:Zellweger Syndrome / Q000235:genetics*
chemical_list: D021901:DNA, Intergenic; D008565:Membrane Proteins; C455539:PEX14 protein, human; D012097:Repressor Proteins