Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders
Zhongyi Zhang
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorCorresponding Author
Yasuyuki Suzuki
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Department of Pediatrics, Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500-8705, Japan; Fax: +81-58-265-9011Search for more papers by this authorNobuyuki Shimozawa
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorSeiji Fukuda
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorAtsushi Imamura
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorToshiro Tsukamoto
Department of Life Science, Himeji Institute of Technology, Hyogo, Japan
Search for more papers by this authorTakashi Osumi
Department of Life Science, Himeji Institute of Technology, Hyogo, Japan
Search for more papers by this authorYukio Fujiki
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan
Search for more papers by this authorTadao Orii
Faculty of Human Welfare, Chubu Gakuin University, Gifu, Japan
Search for more papers by this authorRonald J.A. Wanders
Department of Pediatrics and Clinical Chemistry, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorPeter G. Barth
Department of Pediatrics and Neurology, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorHugo W. Moser
Kennedy-Krieger Institute, Johns Hopkins University, Baltimore, Maryland
Search for more papers by this authorBarbara C. Paton
Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia
Search for more papers by this authorGuy T. Besley
Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, UK
Search for more papers by this authorNaomi Kondo
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorZhongyi Zhang
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorCorresponding Author
Yasuyuki Suzuki
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Department of Pediatrics, Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500-8705, Japan; Fax: +81-58-265-9011Search for more papers by this authorNobuyuki Shimozawa
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorSeiji Fukuda
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorAtsushi Imamura
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorToshiro Tsukamoto
Department of Life Science, Himeji Institute of Technology, Hyogo, Japan
Search for more papers by this authorTakashi Osumi
Department of Life Science, Himeji Institute of Technology, Hyogo, Japan
Search for more papers by this authorYukio Fujiki
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan
Search for more papers by this authorTadao Orii
Faculty of Human Welfare, Chubu Gakuin University, Gifu, Japan
Search for more papers by this authorRonald J.A. Wanders
Department of Pediatrics and Clinical Chemistry, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorPeter G. Barth
Department of Pediatrics and Neurology, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorHugo W. Moser
Kennedy-Krieger Institute, Johns Hopkins University, Baltimore, Maryland
Search for more papers by this authorBarbara C. Paton
Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia
Search for more papers by this authorGuy T. Besley
Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, UK
Search for more papers by this authorNaomi Kondo
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan
Search for more papers by this authorAbstract
The PEX6 (peroxisome assembly factor-2, PAF-2) gene encodes a member of the AAA protein (ATPases associated with diverse cellular activities) family and restores peroxisome assembly in fibroblasts from peroxisome biogenesis disorder patients belonging to complementation group C (group 4 in the United States). We have now clarified the genomic DNA structure of human PEX6 and identified mutations in patients from various ethnic groups. The human PEX6 gene consists of 17 exons and 16 introns, spanning about 14kb. The largest exon, exon 1, has at least 952 bp nucleotides. Eleven novel mutations (18 alleles) were identified by direct sequencing of the PEX6 cDNA from 10 patients. All these mutations have been confirmed in the corresponding genomic DNA. There was no common mutation, but an exon skip was identified in two unrelated Japanese patients. Most of the mutations led to premature termination or large deletions of the PEX6 protein and resulted in the most severe peroxisome biogenesis disorder phenotype of Zellweger syndrome. A patient with an atypical Zellweger syndrome had a missense mutation that was shown to disrupt the cell's ability to form peroxisomes. This mutation analysis will aid in understanding the functions of the PEX6 protein in peroxisomal biogenesis. Hum Mutat 13:487–496, 1999. © 1999 Wiley-Liss, Inc.
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