Abstract
Background: Peroxisome biogenesis disorders (PBDs) may have a variable clinical expression, ranging from severe, lethal to mild phenotypes with progressive evolution. PBDs are autosomal recessive disorders caused by mutations in PEX genes, which encode proteins called peroxins, involved in the assembly of the peroxisome.
Patient Description: We herein report a patient who is currently 9 years old and who is compound heterozygous for two novel mutations in the PEX3 gene.
Results: Mild biochemical abnormalities of the peroxisomal parameters suggested a Zellweger spectrum defect in the patient. Sequence analysis of the PEX3 gene identified two novel heterozygous, pathogenic mutations.
Conclusion: Mutations in PEX3 usually result in a severe, early lethal phenotype. We report a patient compound heterozygous for two novel mutations in the PEX3 gene, who is less affected than previously reported patients with a defect in the PEX3 gene. Our findings indicate that PEX3 defects may cause a disease spectrum similar as previously observed for other PEX gene defects.
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Ebberink MS, Mooijer P, Gootjes J et al (2011) Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder. Hum Mutat 32:59–69
Ebberink MS, Koster J, Visser G et al (2012) A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11β gene. J Med Genet 49:307–313
Ghaedi K, Honsho M, Shimozawa N et al (2000) PEX3 is the causal gene responsible for peroxisome membrane assembly-defective Zellweger syndrome of complementation group G. Am J Hum Genet 67:976–981
Matsui S, Funahashi M, Honda A, Shimozawa N (2013) Newly identified milder phenotype of peroxisome biogenesis disorder caused by mutated PEX3 gene. Brain Dev 35:842–848
Muntau AC, Mayerhofer PU, Paton BC et al (2000a) Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G. Am J Hum Genet 67:967–975
Muntau AC, Holzinger A, Mayerhofer P et al (2000b) The human PEX3 gene encoding a peroxisomal assembly protein: genomic organization, positional mapping, and mutation analysis in candidate phenotypes. Biochem Biophys Res Commun 268:704–710
Regal L, Ebberink M, Goemans N et al (2010) Mutations in PEX10 are a cause of autosomal recessive ataxia. Ann Neurol 68:259–263
Sevin C, Ferdinandusse S, Waterham HR et al (2011) Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene. Orphanet J Rare Dis 10:6–8
Shimozawa N, Nagase T, Takemoto Y et al (2005) Molecular and neurologic findings of peroxisome biogenesis disorders. J Child Neurol 20:326–329
Thoms S, Gärtner J (2012) First PEX11b patient extends spectrum of peroxisomal biogenesis disorder phenotypes. J Med Genet 49:314–316
Wanders RJ (1999) Peroxisomal disorders: clinical, biochemical and molecular aspects. Neurochem Res 24:565–580
Wanders R, Waterham H (2004) Peroxisomal disorders I: biochemistry and genetics of peroxisome biogenesis disorders. Clin Genet 67:107–133
Zeharia A, Ebberink M, Wanders R et al (2007) A novel PEX12 mutation identified as the cause of a peroxisomal biogenesis disorder with mild clinical phenotype, mild biochemical abnormalities in fibroblasts and a mosaic catalase immunofluorescence pattern, even at 40°C. J Hum Genet 52:599–606
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Communicated by: Robert Steiner
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Declaration of Conflicting Interests
Delfina Marchione works for Genzyme Sanofi Company.
The authors Clarisa Maxit, Inés Denzler, Guillermo Agosta, Janet Koster, Ronald Wanders, Sacha Ferdinandusse and Hans Waterham declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
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The authors received no financial support for the research, authorship and/or publication of this article.
Author Contributions
CM, ID, MD and AG: conception, manuscript, acquisition of clinical data, preparation and revision of intellectual content, and final approval of the manuscript. KJ, WRJA, FS and WHR: acquisition of biochemical and genetic data, review and critique, and final approval of the manuscript.
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This work was performed in agreement with the ethical rules of Hospital Italiano de Buenos Aires. No ethical approval was necessary for the writing of this case report.
The authors received an informed consent form from the patient’s parents.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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© 2016 Society for the Study of Inborn Errors of Metabolism (SSIEM)
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Maxit, C. et al. (2016). Novel PEX3 Gene Mutations Resulting in a Moderate Zellweger Spectrum Disorder. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 34. JIMD Reports, vol 34. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_10
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DOI: https://doi.org/10.1007/8904_2016_10
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