Biochemical Features of a Patient with Zellweger-like Syndrome with Normal PTS-1 and PTS-2 Peroxisomal Protein Import Systems: A New Peroxisomal Disease

Singh, Inderjit; Voigt, Robert G.; Sheikh, Faruk; Kremser, K; Brown, Frank R.

doi:10.1006/bmme.1997.2593

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…In this respect, it is interesting to note that Singh et al (1997) have demonstrated that the import of catalase is very important for the metabolic functions of peroxisomes. They suggest that more-mildly affected patients, especially, may import sufficient levels of other peroxisomal enzymes but have a more pronounced defect in catalase import.…”

Section: Misfolding As a Reason For Reduced Pex1 Protein Levels?mentioning

confidence: 99%

Disorders of Peroxisome Biogenesis Due to Mutations in PEX1: Phenotypes and PEX1 Protein Levels

Walter

Gootjes

Mooijer

et al. 2001

The American Journal of Human Genetics

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Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD) are clinically overlapping syndromes, collectively called "peroxisome biogenesis disorders" (PBDs), with clinical features being most severe in ZS and least pronounced in IRD. Inheritance of these disorders is autosomal recessive. The peroxisome biogenesis disorders are genetically heterogeneous, having at least 12 different complementation groups (CGs). The gene affected in CG1 is PEX1. Approximately 65% of the patients with PBD harbor mutations in PEX1. In the present study, we used SSCP analysis to evaluate a series of patients belonging to CG1 for mutations in PEX1 and studied phenotype-genotype correlations. A complete lack of PEX1 protein was found to be associated with severe ZS; however, residual amounts of PEX1 protein were found in patients with the milder phenotypes, NALD and IRD. The majority of these latter patients carried at least one copy of the common G843D allele. When patient fibroblasts harboring this allele were grown at 30 degrees C, a two- to threefold increase in PEX1 protein levels was observed, associated with a recovery of peroxisomal function. This suggests that the G843D missense mutation results in a misfolded protein, which is more stable at lower temperatures. We conclude that the search for the factors and/or mechanisms that determine the stability of mutant PEX1 protein by high-throughput procedures will be a first step in the development of therapeutic strategies for patients with mild PBDs.

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Section: Misfolding As a Reason For Reduced Pex1 Protein Levels?mentioning

confidence: 99%

Disorders of Peroxisome Biogenesis Due to Mutations in PEX1: Phenotypes and PEX1 Protein Levels

Walter

Gootjes

Mooijer

et al. 2001

The American Journal of Human Genetics

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“…However, the peroxisomal enzyme catalase detoxifies H 2 O 2 to water and molecular oxygen 2. Lack of detoxification of H 2 O 2 in peroxisomes as a result of absence of catalase targeting to peroxisomes (catalase-negative peroxisomes) was described in patients with progressive developmental delay, micronodular cirrhosis, and elevated very-long-chain fatty acids in plasma and skin fibroblasts 6. Inherited abnormalities in peroxisomal β-oxidation such as X-adrenoleukodystrophy (X-ALD) leads to progressive inflammatory demyelinating disease (Figure 1D).…”

Section: Introductionmentioning

confidence: 99%

“…2 Lack of detoxification of hydrogen peroxide in peroxisomes as a result of absence of catalase targeting to peroxisomes (catalase-negative peroxisomes) was described in patients with progressive developmental delay, micronodular cirrhosis, and elevated very-long-chain fatty acids in plasma and skin fibroblasts. 7 Moreover, inherited abnormalities in peroxisomal b-oxidation such as X-adrenoleukodystrophy lead to progressive inflammatory demyelinating disease (Figure 1D). 8 In addition to catabolic and detoxifying functions, peroxisomes participate in the synthesis of important membrane structural components such as plasmalogens, long-chain alcohol, and n-3/n-6 polyunsaturated fatty acids.…”

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confidence: 99%

Peroxisomal Dysfunction in Inflammatory Childhood White Matter Disorders: An Unexpected Contributor to Neuropathology

Singh

Contreras

2009

J Child Neurol

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Peroxisome, a ubiquitous subcellular organelle, plays an important function in cellular metabolism, and its importance for human health is underscored by the identification of fatal disorders caused by genetic abnormalities. Recent findings indicate that peroxisomal dysfunction is not restricted only to inherited peroxisomal diseases but also to disease processes associated with generation of inflammatory mediators that downregulate cellular peroxisomal homeostasis. Evidence indicates that leukodystrophies (X-linked adrenoleukodystrophy, globoid cell leukodystrophy, periventricular leukomalacia) may share common denominators in the development and progression of the inflammatory process and thus in the dysfunctions of peroxisomes. Dysfunctions of peroxisomes may therefore contribute in part to white matter disease and to the mental and physical disabilities that develop in patients affected by these diseases.

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Lexikalischer Teil

Witkowski

Prokop

Ullrich³

et al. 2003

Lexikon Der Syndrome Und Fehlbildungen

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Biochemical Features of a Patient with Zellweger-like Syndrome with Normal PTS-1 and PTS-2 Peroxisomal Protein Import Systems: A New Peroxisomal Disease

Cited by 8 publications

References 27 publications

Disorders of Peroxisome Biogenesis Due to Mutations in PEX1: Phenotypes and PEX1 Protein Levels

Disorders of Peroxisome Biogenesis Due to Mutations in PEX1: Phenotypes and PEX1 Protein Levels

Peroxisomal Dysfunction in Inflammatory Childhood White Matter Disorders: An Unexpected Contributor to Neuropathology

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