Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.

[neonatal adrenoleukodystrophy]

Human peroxisome biogenesis disorders (PBDs ) are a group of genetically heterogeneous autosomal-recessive disease caused by mutations in PEX genes that encode peroxins , proteins required for peroxisome biogenesis . These lethal diseases include Zellweger syndrome (ZS ), neonatal adrenoleukodystrophy (NALD ) and infantile Refsum 's disease (IRD ), three phenotypes now thought to represent a continuum of clinical features that are most severe in ZS , milder in NALD and least severe in IRD 2 . At least eleven PBD complementation groups have been identified by somatic-cell hybridization analysis compared to the eighteen PEX complementation groups that have been found in yeast . We have cloned the human PEX 1 gene encoding a 147 -kD member of the AAA protein family (ATPases associated with diverse cellular activities ), which is the putative orthologue of Saccharomyces cerevisiae Pex 1 p (ScPex 1 p ). Human PEX 1 has been identified by computer-based 'homology probing ' using the ScPex 1 p sequence to screen databases of expressed sequence tags (dbEST ) for human cDNA clones . Expression of PEX 1 rescued the cells from the biogenesis defect in human fibroblasts of complementation group 1 (CG 1 ), the largest PBD complementation group . We show that PEX 1 is mutated in CG 1 patients .