title: A novel aberrant splicing mutation of the PEX16 gene in two patients with Zellweger syndrome.
abstract: Human Pex16p, a peroxisomal membrane protein composed of 336 amino acids, plays a central role in peroxisomal membrane biogenesis. A nonsense mutation (R176ter) in the PEX16 gene has been reported in the case of only one patient (D-01) belonging to complementation group D of the peroxisome biogenesis disorders. We have now identified two patients belonging to group D (D-02 and D-03) whose fibroblasts were found to contain no peroxisomal membrane structure ghosts. Molecular analysis of the PEX16 gene revealed aberrant cDNA species lacking 65 bp, corresponding to exon 10 skipping caused by a splice site mutation (IVS10 + 2T -->C). Both patients, although unrelated, were homozygous for this mutation. This mutation changes the amino acid sequence starting from codon 298 and introduces a termination codon at codon 336. As a consequence, the cell's ability to membrane synthesis and protein import is disrupted, which implies that the changed C terminus of the Pex16p in these patients likely affects its function.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Gifu 500-8076, Japan. nshim@cc.gifu-u.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nagase
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiki
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
mesh_terms: D018528:ATP-Binding Cassette Transporters; D017398:Alternative Splicing; D001483:Base Sequence; D002374:Catalase / Q000032:analysis / Q000276:immunology; D002460:Cell Line; D004252:DNA Mutational Analysis; D005347:Fibroblasts / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D014162:Transfection; D015211:Zellweger Syndrome / Q000235:genetics* / Q000473:pathology
chemical_list: C063305:ABCD3 protein, human; D018528:ATP-Binding Cassette Transporters; D005656:Fungal Proteins; D008565:Membrane Proteins; C486345:PEX16 protein, human; D002374:Catalase