PEX7 Gene

The PEX7 gene (PEX7 stands for Peroxisomal Biogenesis Factor 7) is a protein coding gene located on chromosome 6q23.3. The PEX7 gene encodes the cytosolic receptor for a series of peroxisomal matrix enzymes that are targeted to the organelle by peroxisome targeting signal 2 (PTS2). Defects in this gene cause peroxisome biogenesis (PBD) disorders characterized by multiple defects in peroxisome function. Although the clinical features of PBD patients vary, the cells of all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle.

Mutations in the PEX7 gene are associated with complementation group 11 (PBD-CG11) PBD disorders:

• rhizomelic chondrodysplasia punctata type 1 (RCDP1).
• Refsum syndrome (RD).

Patients suffering from Refsum syndrome (RD) have elevated levels of phytanic acid due to a deficiency of the peroxisomal enzyme phytanoyl-CoA hydroxylase (PhyH). Disease-causing mutations in the PHYH gene have been identified in most patients with RD. In another proportion, mutations are detected in the PEX7 gene. This encodes the peroxin-7 receptor protein, which is required for peroxisomal import of proteins with a type 2 peroxisomal targeting signal.

Mutations in PEX7 usually cause rhizomelic chondrodysplasia punctata type 1, a severe peroxisomal disorder. However, biochemical analysis of patients with RD revealed defects not only in phytanic acid alpha-oxidation but also in peroxisomal thiolase. Mutations in the PEX7 gene can thus lead to a broad clinical spectrum ranging from severe rhizomelic chondrodysplasia punctata to a relatively mild refsum syndrome.