A novel aberrant splicing mutation of the PEX16 gene in two patients with Zellweger syndrome |
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Authors: | Shimozawa Nobuyuki Nagase Tomoko Takemoto Yasuhiko Suzuki Yasuyuki Fujiki Yukio Wanders Ronald J A Kondo Naomi |
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Institution: | Department of Pediatrics, Gifu University School of Medicine, Gifu 500-8076, Japan. nshim@cc.gifu-u.ac.jp |
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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. |
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Keywords: | peroxisome biogenesis disorders PEX16 Zellweger syndrome peroxisomal membrane protein splice site mutation |
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