Disorders of peroxisome biogenesis: complementation analysis shows genetic heterogeneity with strong overrepresentation of one group (PEX1 deficiency).

Abstract

The peroxisomal disorders represent a group of genetic diseases in man in which there is an impairment in one or more peroxisomal functions (Wanders et al 1995). One group of peroxisomal disorders involves the disorders of peroxisome biogenesis (PBDs), which include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD) plus a number of phenotypic variants not easily assignable to one of these entities. In addition to these disorders, rhizomelic chondrodysplasia punctata (RCDP) type 1 should also be included in the group of biogenesis disorders. In RCDP type I there is a selective defect in the import of a group of peroxisomal proteins with a peroxisome-targeting signal type 2 (PTS2) motif due to mutations in the PEX7 gene coding for the PTS2-receptor (Braverman et al 1997; Motley et al 1997; Purdue et al 1997). Earlier studies have already revealed genetic heterogeneity among patients affected by disorders of peroxisome biogenesis (Brul et al 1988; McGuiness et al 1990; Moser et al 1995; Poll-The et al 1989; Roscher et al 1989; Shimozawa et al 1993; Yajima et al 1992). We have now extended these studies to 113 patients by performing complementation analysis in fibroblasts using catalase immunofluorescence as a parameter for complementation.