title: Identification of a novel PEX14 mutation in Zellweger syndrome.
abstract: 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]).
authors.affiliation: K.U.Leuven, Moleculaire Celbiologie, Campust Gasthuisberg ON1, Herestraat 49 box 601, Leuven, 3000, Belgium.
authors.forename: Sofie J
authors.initials: SJ
authors.lastname: Huybrechts
authors.forename: Paul P
authors.initials: PP
authors.lastname: Van Veldhoven
authors.forename: Ilse
authors.initials: I
authors.lastname: Hoffman
authors.forename: Renate
authors.initials: R
authors.lastname: Zeevaert
authors.forename: Rita
authors.initials: R
authors.lastname: de Vos
authors.forename: Philippe
authors.initials: P
authors.lastname: Demaerel
authors.forename: Marijke
authors.initials: M
authors.lastname: Brams
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
authors.forename: Marc
authors.initials: M
authors.lastname: Fransen
authors.forename: David
authors.initials: D
authors.lastname: Cassiman