Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders

The PEX6 (peroxisome assembly factor-2, PAF-2) gene encodes a member of the AAA protein (ATPases associated with diverse cellular activities) family a cid restores peroxisome assembly in fibroblasts from peroxisome biogenesis disorder patients belonging to complementation group C (group 4 in the Unit ed States). We have now clarified the genomic DNA structure of human PEX6 a nd identified mutations in patients from various ethnic groups. The human P EX6 gene consists of 17 exons and 16 introns, spanning about 14kb, The larg est 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 p atients. All these mutations have been confirmed in the corresponding genom ic DNA, There was no common mutation, but an exon skip was identified in tw o unrelated Japanese patients. Most of the mutations led to premature termi nation or large deletions of the PEX6 protein and resulted in the most seve re peroxisome biogenesis disorder phenotype of Zellweger syndrome. A patien t with an atypical Zellweger syndrome had a missense mutation that was show n 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, (C) 1999 Wiley-Liss, Inc.