CORRECTION BY GENE-EXPRESSION OF BIOCHEMICAL-ABNORMALITIES IN FIBROBLASTS FROM ZELLWEGER PATIENTS

Zellweger syndrome is a prototype of peroxisomal biogenesis disorders and a fatal autosomal recessive disease with no effective therapy. We identified nine genetic complementation groups of these disorders, and mutations in peroxisome assembly factor-1 (PAF-1) and the 70-kD perox isomal membrane protein (PMP70) genes have been detected by our group F and Roscher's group 1, respectively. We now describe permanent recov ery from generalized peroxisomal abnormalities in fibroblasts of a Zel lweger patient from group F, such as biochemical defects of peroxisoma l beta-oxidation, plasmalogen biosynthesis, and morphologic absence of peroxisomes, by stable transfection of human cDNA encoding PAF-1. In the light these observations, we designed a gene expression system fib roblasts from patients with peroxisomal biogenesis disorders. In Zellw eger fibroblasts obtained from Roscher's group 1 and transfected with human cDNA encoding PMP70, peroxisomes were not morphologically identi fiable, and peroxisomal function did not normalize.