Identification of PEX7 as the Second Gene Involved in Refsum Disease
| Autor: | John Mitchell, Ronald J.A. Wanders, Daan M. van den Brink, Janet Haasjes, Michelle Lambert-Hamill, Pedro Brites, Gerbert A. Jansen, Anthony S. Wierzbicki, Hans R. Waterham, Jacqueline de Belleroche |
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| Rok vydání: | 2003 |
| Předmět: | |
| Zdroj: | Advances in Experimental Medicine and Biology ISBN: 9781461347828 ResearcherID |
| Popis: | 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 α-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. |
| Databáze: | OpenAIRE |
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