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Title: Identification of a novel PEX14 mutation in Zellweger syndrome
Authors: Huybrechts, Sofie
Van Veldhoven, Paul P
Hoffman, Ilse
Zeevaert, Renate
De Vos, Rita
Demaerel, Philippe
Brams, Marijke
Jaeken, Jacques
Fransen, Marc ×
Cassiman, David #
Issue Date: 29-Feb-2008
Publisher: British Medical Association
Series Title: Journal of Medical Genetics vol:45 issue:6 pages:376-383
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. METHODS AND RESULTS: Here we report a patient with Zellweger syndrome, who presented at the age of three months with icterus, dystrophy, axial hypotonia, facial dysmorphy, posterior embryotoxon, and hepatomegaly. Abnormal findings of metabolic screening tests included hyperbilirubinemia, hypoketotic dicarboxylic aciduria, increased C26:0 and decreased C22:0 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.
URI: 
ISSN: 0022-2593
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Structural Neurobiology
Hepatology
Section Child - Miscellaneous (-)
Translational Cell & Tissue Research
Radiology
Pharmacology Section (-)
Laboratory of Lipid Biochemistry and Protein Interactions
Translational MRI (+)
× corresponding author
# (joint) last author

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