PT  - JOURNAL ARTICLE
AU  - S J Huybrechts
AU  - P P Van Veldhoven
AU  - I Hoffman
AU  - R Zeevaert
AU  - R de Vos
AU  - P Demaerel
AU  - M Brams
AU  - J Jaeken
AU  - M Fransen
AU  - D Cassiman
TI  - Identification of a novel <em>PEX14</em> mutation in Zellweger syndrome
AID  - 10.1136/jmg.2007.056697
DP  - 2008 Jun 01
TA  - Journal of Medical Genetics
PG  - 376--383
VI  - 45
IP  - 6
4099  - http://jmg.bmj.com/content/45/6/376.short
4100  - http://jmg.bmj.com/content/45/6/376.full
SO  - J Med Genet2008 Jun 01; 45
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.