PT - JOURNAL ARTICLE AU - Sofie J Huybrechts AU - Paul P Van Veldhoven AU - Ilse Hoffman AU - Renate Zeevaert AU - Rita de Vos AU - Philippe Demaerel AU - Marijke Brams AU - Jaak Jaeken AU - Marc Fransen AU - David Cassiman TI - Identification of a novel <em>PEX14</em> mutation in Zellweger syndrome AID - 10.1136/bcr.07.2008.0503 DP - 2009 Jan 01 TA - BMJ Case Reports PG - bcr0720080503 VI - 2009 4099 - http://casereports.bmj.com/content/2009/bcr.07.2008.0503.short 4100 - http://casereports.bmj.com/content/2009/bcr.07.2008.0503.full AB - Here we report a patient with Zellweger syndrome, who presented at the age of 3 months with icterus, dystrophy, axial hypotonia, and hepatomegaly. Abnormal findings of metabolic screening tests included hyperbilirubinaemia, hypoketotic dicarboxylic aciduria, increased C26:0 and decreased C22:0 plasma levels, and strongly reduced plasmalogen concentrations. In fibroblasts, both peroxisomal α- and β-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. 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]).