Open AccessIdentification of a novel PEX14 mutation in Zellweger syndrome
Author(s) -
Sofie Huybrechts,
Paul P. Van Veldhoven,
Ilse Hoffman,
Renate Zeevaert,
Rita De Vos,
Philippe Demaerel,
Marijke Brams,
Jaak Jaeken,
Marc Fransen,
David Cassiman
Publication year - 2009
Publication title -
bmj case reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.231
H-Index - 26
ISSN - 1757-790X
DOI - 10.1136/bcr.07.2008.0503
Subject(s) - zellweger syndrome , plasmalogen , hypotonia , peroxisome , peroxisomal disorder , endocrinology , exon , medicine , microbiology and biotechnology , biology , pathology , gene , genetics , phospholipid , membrane , receptor
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 C(26:0) and decreased C(22:0) 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]).