Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized impairment of peroxisomal functions. A study using complementation analysis.

Abstract

We have used complementatiod analysis after somatic cell fu- sion' to investigate the genetic relationships among various ge- netic diseases in humans in which there is a simultaneous im- pairment of several peroxisomal functions. The activity of acyl-coeizyme A:dihydroxyacetonephosphate acyltransferase, whici is deficient in these diseases, was used as an index of complementation. In some of these diseases peroxisomes are deficient and catalase is present in the cytosol, so that the appearance of particle-bound catalase could be used as an index of complementation. The cell lines studied can be divided into at least five complementation groups. Group 1 is repre- 46nted by a cell line from a patient with the rhizomelic form of chondrodysplasia punctata. Group 2 consists of cell lines from fbur patients with the Zellweger syndrome, a patient with the ihfantile form of Refsum disease and a patient with hyperpipe- colic acidemia. Group 3 comprises one cell line from a patient with the Zellweger syndrome, group 4 one cell line from a patient with the neonatal form of adrenoleukodystrophy, and group 5 one cell line from a patient with the Zellweger syn- drome. We conclude that at least five genes are required for the assembly of a functional peroxisome.