RT Journal Article
SR Electronic
T1 Identification of a novel <em>PEX14</em> mutation in Zellweger syndrome
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 376
OP 383
DO 10.1136/jmg.2007.056697
VO 45
IS 6
A1 S J Huybrechts
A1 P P Van Veldhoven
A1 I Hoffman
A1 R Zeevaert
A1 R de Vos
A1 P Demaerel
A1 M Brams
A1 J Jaeken
A1 M Fransen
A1 D Cassiman
YR 2008
UL http://jmg.bmj.com/content/45/6/376.abstract
AB 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 3 months with icterus, dystrophy, axial hypotonia, facial dysmorphy, posterior embryotoxon, 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, 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.