Identification of a novel PEX14 mutation in Zellweger syndrome

• Published in: BMJ case reports Vol. 2009; no. jan21 1; p. bcr0720080503
• Main Authors: Huybrechts, Sofie J, Van Veldhoven, Paul P, Hoffman, Ilse, Zeevaert, Renate, de Vos, Rita, Demaerel, Philippe, Brams, Marijke, Jaeken, Jaak, Fransen, Marc, Cassiman, David
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 2009; BMJ Publishing Group
• Series: Findings that shed new light on the possible pathogenesis of a disease or an adverse effect
• Subjects: Age; Biopsy; Biosynthesis; Enzymes; Europe (West); Fatty acids; Fibroblasts; Findings That Shed New Light on the Possible Pathogenesis of a Disease or an Adverse Effect; Gallbladder diseases; Genes; Indian Sub-Continent; Liver; Male; Metabolism; Microscopy; Mutation; Neonate; Oxidation; Patients; Phosphatase
• ISSN: 1757-790X; 1757-790X
• DOI: 10.1136/bcr.07.2008.0503

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]).