PEX3 is the causal gene responsible for peroxisome membrane assembly-defective Zellweger syndrome of complementation group G.

[neonatal adrenoleukodystrophy]

Peroxisome biogenesis disorders (PBDs ) such as Zellweger syndrome (ZS ) and neonatal adrenoleukodystrophy are autosomal recessive diseases caused by defects in peroxisome assembly , for which 13 genotypes have been identified . Expression of the human peroxin Pex 3 p cDNA encoding a 373 -amino-acid peroxisomal membrane protein morphologically and biochemically restored peroxisome biogenesis , including peroxisomal membrane assembly , in fibroblasts from PBDG-02 , a patient with complementation group G (CG-G ) ZS . Patient PBDG-02 carried a homozygous , inactivating mutation -a 97 -bp deletion of nucleotide residues at positions 942 -1038 -resulting in a 32 -amino-acid truncation and in a frameshift inducing both a 3 -amino-acid substitution and a termination codon . Genomic PCR analysis revealed mutation of T -->G at eight bases upstream of the splicing site at the boundary of intron 10 and exon 11 of PEX 3 gene , giving rise to a deletion of all of exon 11 . When assessed by expression in a pex 3 mutant of Chinese hamster ovary cells and the patient 's fibroblasts , PBDG-02 -derived PEX 3 cDNA was found to be defective in peroxisome-restoring activity . These results provide evidence that PEX 3 is a novel , pathogenic gene responsible for CG-G PBDs .