Abstract |
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.
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Authors | Daan M van den Brink, Pedro Brites, Janet Haasjes, Anthony S Wierzbicki, John Mitchell, Michelle Lambert-Hamill, Jacqueline de Belleroche, Gerbert A Jansen, Hans R Waterham, Ronald J A Wanders |
Journal | American journal of human genetics
(Am J Hum Genet)
Vol. 72
Issue 2
Pg. 471-7
(Feb 2003)
ISSN: 0002-9297 [Print] United States |
PMID | 12522768
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 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
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Topics |
- Acetyl-CoA C-Acetyltransferase
(genetics, metabolism)
- Adult
- Alleles
- Cells, Cultured
- Chromosomes, Human, Pair 6
- Female
- Fibroblasts
(cytology, enzymology)
- Genetic Linkage
- Humans
- Male
- Mixed Function Oxygenases
(genetics, metabolism)
- Mutation
- Peroxisomal Targeting Signal 2 Receptor
- Phytanic Acid
(blood)
- Plasmalogens
(biosynthesis, genetics)
- Receptors, Cytoplasmic and Nuclear
(genetics)
- Refsum Disease
(genetics, pathology, physiopathology)
- Siblings
- Skin
(cytology)
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