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Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor‐2) gene in patients with peroxisome biogenesis disorders
Author(s) -
Zhang Zhongyi,
Suzuki Yasuyuki,
Shimozawa Nobuyuki,
Fukuda Seiji,
Imamura Atsushi,
Tsukamoto Toshiro,
Osumi Takashi,
Fujiki Yukio,
Orii Tadao,
Wanders Ronald J.A.,
Barth Peter G.,
Moser Hugo W.,
Paton Barbara C.,
Besley Guy T.,
Kondo Naomi
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1999)13:6<487::aid-humu9>3.0.co;2-t
Subject(s) - biology , zellweger syndrome , genetics , exon , peroxisomal disorder , missense mutation , mutation , gene , peroxisome , microbiology and biotechnology
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.