Abstract
The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous diseases lethal in early infancy1. Although the clinical features of PBD patients may vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins. This cellular phenotype is shared by yeast pex mutants, and human orthologues of yeast PEX genes have been shown to be defective in some groups of PBD patients2,3. We identified a putative human orthologue of ScPEX12 by screening the database of expressed sequence tags for cDNAs capable of encoding a protein similar to yeast Pex12p4. Although its sequence similarity to yeast Pex 12 proteins was limited, PEX12 shared the same subcellular distribution as yeast Pex12p and localized to the peroxisome membrane. PEX12 expression restored peroxisomal protein import in fibroblasts from PBD patients of complement group 3 (CG3) and frameshift mutations in PEX12 were detected in two unrelated CG3 patients. These data demonstrate that mutations in PEX12 are responsible for CG3 of the PBD and that PEX12 plays an essential role in peroxisomal matrix protein import.
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Chang, CC., Lee, WH., Moser, H. et al. Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders. Nat Genet 15, 385–388 (1997). https://doi.org/10.1038/ng0497-385
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DOI: https://doi.org/10.1038/ng0497-385
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