Identification of PEX7 as the second gene involved in Refsum disease
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Peripheral neuropathy has been reported in a clinical subset of RCDP patients.
“In line with myelination defects also in the PNS, peripheral neuropathy has been reported in a clinical subset of RCDP patients [201].”
From Peroxisomes in brain development and function (2016) · cites this paper as [201]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Metabolic and Molecular Bases of Inherited Disease
Scriver, R. C. (1995) · Medical Entomology and Zoology · Cited by 12,101 · see citing works
The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928 · see citing works
Parametric and nonparametric linkage analysis: a unified multipoint approach.
Kruglyak, L., Daly, M. J., Daly, M. J., & Lander, E. S. (1996) · PubMed Central · Cited by 2,883 · see citing works
Swinkels, B. W., Gould, S. J., Bodnar, A. G., Rachubinski, R. A., & Subramani, S. E. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04889.x · Cited by 623 · see citing works
Braverman, N., Steel, G., Obie, C., Moser, A. B., Moser, H. W., Gould, S. J., & Valle, D. L. (1997) · Nature Genetics · doi:10.1038/ng0497-369 · Cited by 433 · see citing works
Techniques in diagnostic human biochemical genetics
Shapira, E. (1991) · Europe PMC (PubMed Central) · Cited by 351 · see citing works
Refsum disease is caused by mutations in the phytanoyl–CoA hydroxylase gene
Jansen, G. A., Oftnan, R., Ferdinandusse, S., IJlst, L., Muijsers, A. O., Skjeldal, O. H., Stokke, O., Jakobs, C., BESLEY, G. T. N., Wraith, J. E., et al. (1997) · Nature Genetics · doi:10.1038/ng1097-190 · Cited by 306 · see citing works
Self-citationMotley, A. M., Hettema, E. H., Hogenhout, E. M., Brites, P., ten Asbroek, A. L. M. A., Wijburg, F. A., Baas, F., Heijmans, H. S. A., Tabak, H. F., Wanders, R. J. A., et al. (1997) · Nature Genetics · doi:10.1038/ng0497-377 · Cited by 271 · see citing works
Self-citationPurdue, P. E., Zhang, J. W., Skoneczny, M., & Lazarow, P. B. (1997) · Nature Genetics · doi:10.1038/ng0497-381 · Cited by 265 · see citing works
Identification of PAHX, a Refsum disease gene
Mihalik, S. J., Morrell, J. C., Kim, D., Sacksteder, K. A., Watkins, P. A., & Gould, S. J. (1997) · Nature Genetics · doi:10.1038/ng1097-185 · Cited by 244 · see citing works
Refsum's disease: a peroxisomal disorder affecting phytanic acid α‐oxidation
Wierzbicki, A. S., Lloyd, M. D., Schofield, C. J., Feher, M. D., & Gibberd, F. B. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00766.x · Cited by 190 · see citing works
Self-citationBraverman, N., Chen, L., Lin, P., Obie, C., Steel, G., Douglas, P., Chakraborty, P. K., Clarke, J. T. R., Boneh, A., Moser, A., et al. (2002) · Human Mutation · doi:10.1002/humu.10124 · Cited by 134 · see citing works
Biochemical abnormalities in rhizomelic chondrodysplasia punctata
Hoefler, G., Hoefler, S., Watkins, P. A., Chen, W. W., Moser, A., Baldwin, V., McGillivary, B., Charrow, J., Friedman, J. M., Rutledge, L., et al. (1988) · The Journal of Pediatrics · doi:10.1016/s0022-3476(88)80689-9 · Cited by 133 · see citing works
The peroxisome biogenesis disorders
Gould, S. (2001) · Medical Entomology and Zoology · Cited by 127 · see citing works
Motley, A. M., Brites, P., Gerez, L., Hogenhout, E., Haasjes, J., Benne, R., Tabak, H. F., Wanders, R. J. A., & Waterham, H. R. (2002) · The American Journal of Human Genetics · doi:10.1086/338998 · Cited by 107 · see citing works
Self-citationRefsum Disease, Peroxisomes and Phytanic Acid Oxidation: A Review
Wanders, R. J. A., Jansen, G. A., & Skjeldal, O. H. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.11.1021 · Cited by 106 · see citing works
Self-citationBrown, P. J., Mei, G., Gibberd, F. B., et al. (1993) · Journal of Human Nutrition and Dietetics · doi:10.1111/j.1365-277x.1993.tb00375.x · Cited by 95 · see citing works
Measurement of peroxisomal fatty acid β‐oxidation in cultured human skin fibroblasts
Wanders, R. J. A., Denis, S. W., Ruiter, J. P. N., Schutgens, R. B. H., van Roermund, C. W. T., & Jacobs, B. S. (1995) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711434 · Cited by 95 · see citing works
Plasmalogen biosynthesis in peroxisomal disorders: fatty alcohol versus alkylglycerol precursors.
Schrakamp, G., Schalkwijk, C., Schutgens, R. B. H., Wanders, R. J. A., Tager, J. M., & van den BOSCH, H. (1988) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38538-2 · Cited by 81 · see citing works
Jansen, G. A. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.8.1195 · Cited by 78 · see citing works
Self-citationStructure-function analysis of phytanoyl-CoA 2-hydroxylase mutations causing Refsum's disease
Mukherji, M. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.18.1971 · Cited by 70 · see citing works
Smeitink, J. A. M., Beemer, F. A., Espeel, M., Donckerwocke, R. A. M. G., Jakobs, C., Wanders, R. J. A., Schutgens, R. B. H., Roels, F., Durán, M., DORLAND, L., et al. (1992) · Journal of Inherited Metabolic Disease · doi:10.1007/bf02435981 · Cited by 59 · see citing works
Studies on phytanic acid α-oxidation in rat liver and cultured human skin fibroblasts
Wanders, R. J. A., & van Roermund, C. W. T. (1993) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(93)90239-6 · Cited by 57 · see citing works
Heikoop, J. C., van Roermund, C. W. T., Just, W. W., Ofman, R., Schutgens, R. B. H., Heymans, H. S. A., Wanders, R. J. A., & Tager, J. M. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114674 · Cited by 57 · see citing works
Refsum disease: The presentation and ophthalmic aspects of Refsum disease in a series of 23 patients
Claridge, K. G., Gibberd, F. B., & Sidey, M. C. (1992) · Eye · doi:10.1038/eye.1992.76 · Cited by 54 · see citing works
Purdue, P. E., Skoneczny, M., Yang, X., Zhang, J.-W., & Lazarow, P. B. (1999) · Neurochemical Research · doi:10.1023/a:1023957110171 · Cited by 49 · see citing works
Braverman, N., Steel, G., Lin, P., Moser, A. B., Moser, H. W., & Valle, D. L. (2000) · Genomics · doi:10.1006/geno.1999.6080 · Cited by 47 · see citing works
Identification of genetic heterogeneity in Refsum's disease
Wierzbicki, A. S., Mitchell, J. J., Lambert‐Hammill, M., Hancock, M., Greenwood, J., Sidey, M. C., de Belleroche, J., & Gibberd, F. B. (2000) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200511 · Cited by 42 · see citing works
Self-citationten Brink, H., Schor, D. S. M., Kok, R., et al. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41399-9 · Cited by 37 · see citing works
A new type of chondrodysplasia punctata associated with peroxisomal dysfunction
Poll‐The, B. T., Maroteaux, P., Narcy, C., Quetin, P., Guesnu, M., Wanders, R. J. A., Schutgens, R. B. H., & Saudubray, J. M. (1991) · Journal of Inherited Metabolic Disease · doi:10.1007/bf01811703 · Cited by 32 · see citing works
Skeletal abnormalities in Refsum's disease (heredopathia atactica polyneuritiformis)
Plant, G. R., Hansell, D. M., Gibberd, F. B., & Sidey, M. C. (1990) · British Journal of Radiology · doi:10.1259/0007-1285-63-751-537 · Cited by 29 · see citing works
de Vet, E. C. J. M., Biermann, J., & van den BOSCH, H. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00511.x · Cited by 25 · see citing works
Heikoop, J. C., van den Berg, M., Anneke, S., et al. (1991) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(91)90025-5 · Cited by 21 · see citing works
Gangarossa, S., Mattina, T., Romano, V., Milana, G., Mollica, F., & Schilirò, G. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960315)62:2 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The cornified envelope: a model of cell death in the skin
Candi, E., Schmidt, R., & Melino, G. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1619 · Cited by 1,776 · see citing works
Functions of plasmalogen lipids in health and disease
Braverman, N. E., & Moser, A. B. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.05.008 · Cited by 1,082 · see citing works
Peroxisome biogenesis disorders
Steinberg, S. J., Dodt, G., Raymond, G. V., Braverman, N. E., Moser, A. B., & Moser, H. W. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.09.010 · Cited by 522 · see citing works
Peroxisomes in brain development and function
Berger, J., Dorninger, F., Forss-Petter, S., & Kunze, M. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.12.005 · Cited by 194 · see citing works
Clinical diagnosis, biochemical findings and MRI spectrum of peroxisomal disorders
Poll-The, B. T., & Gärtner, J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.03.011 · Cited by 85 · see citing works
Systemic Diseases Associated with Retinal Dystrophies
Werdich, X. Q., Place, E. M., & Pierce, E. A. (2014) · Seminars in Ophthalmology · doi:10.3109/08820538.2014.959202 · Cited by 54 · see citing works
- Authors
- van den Brink, D. M., Brites, P., Haasjes, J., Wierzbicki, A. S., Mitchell, J., Lambert-Hamill, M., de Belleroche, J., Jansen, G. A., Waterham, H. R., & Ronald Wanders, J. A.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- St Thomas' Hospital (GB)
- Charing Cross Hospital (GB)
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 72
- Issue
- 2
- Pages
- 471-477
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC379239
- OpenAlex
- W2096184116
- Cited by
- 171
- References
- 34
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 3 · 2022: 6 · 2021: 7 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 6 · 2016: 10 · 2015: 4 · 2014: 9 · 2013: 4 · 2012: 10
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Refsum disease, PEX7, phytanic acid, peroxisomal disorders, rhizomelic chondrodysplasia punctata, plasmalogen synthesis, genetic heterogeneity, retinitis pigmentosa, ataxia, polyneuropathy, peroxisomal import
- MeSH terms
- Peroxisomal Targeting Signal 2 Receptor, Acetyl-CoA C-Acetyltransferase, Adult, Alleles, Cells, Cultured, Chromosomes, Human, Pair 6, Female, Fibroblasts, Humans, Mixed Function Oxygenases, Genetic Linkage, Male, Mutation, Phytanic Acid, Plasmalogens, Refsum Disease, Skin, Receptors, Cytoplasmic and Nuclear, Siblings
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
