Identification of PEX7 as the second gene involved in Refsum disease

Am J Hum Genet. 2003 Feb;72(2):471-7. doi: 10.1086/346093. Epub 2003 Jan 9.


Patients affected with Refsum disease (RD) have elevated levels of phytanic acid due to a deficiency of the peroxisomal enzyme phytanoyl-CoA hydroxylase (PhyH). In most patients with RD, disease-causing mutations in the PHYH gene have been identified, but, in a subset, no mutations could be found, indicating that the condition is genetically heterogeneous. Linkage analysis of a few patients diagnosed with RD, but without mutations in PHYH, suggested a second locus on chromosome 6q22-24. This region includes the PEX7 gene, which codes for the peroxin 7 receptor protein required for peroxisomal import of proteins containing a peroxisomal targeting signal type 2. Mutations in PEX7 normally cause rhizomelic chondrodysplasia punctata type 1, a severe peroxisomal disorder. Biochemical analyses of the patients with RD revealed defects not only in phytanic acid alpha-oxidation but also in plasmalogen synthesis and peroxisomal thiolase. Furthermore, we identified mutations in the PEX7 gene. Our data show that mutations in the PEX7 gene may result in a broad clinical spectrum ranging from severe rhizomelic chondrodysplasia punctata to relatively mild RD and that clinical diagnosis of conditions involving retinitis pigmentosa, ataxia, and polyneuropathy may require a full screen of peroxisomal functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA C-Acetyltransferase / genetics
  • Acetyl-CoA C-Acetyltransferase / metabolism
  • Adult
  • Alleles
  • Cells, Cultured
  • Chromosomes, Human, Pair 6
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / enzymology
  • Genetic Linkage
  • Humans
  • Male
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / metabolism
  • Mutation
  • Peroxisomal Targeting Signal 2 Receptor
  • Phytanic Acid / blood
  • Plasmalogens / biosynthesis
  • Plasmalogens / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Refsum Disease / genetics*
  • Refsum Disease / pathology
  • Refsum Disease / physiopathology
  • Siblings
  • Skin / cytology


  • PEX7 protein, human
  • Peroxisomal Targeting Signal 2 Receptor
  • Plasmalogens
  • Receptors, Cytoplasmic and Nuclear
  • Phytanic Acid
  • Mixed Function Oxygenases
  • PHYH protein, human
  • Acetyl-CoA C-Acetyltransferase