Genomic structure of PEX13, a candidate peroxisome biogenesis disorder gene

The peroxisome biogenesis disorders (PBDs) are a set of lethal genetic dise ases characterized by peroxisomal metabolic deficiencies, multisystem abnor malities, mental retardation, and premature death. These disorders are gene tically heterogeneous and are caused by mutations in genes, termed PEX gene s, required for import of proteins into the peroxisomal matrix, We have pre viously reported the identification of human PEX13, the gene encoding the d ocking factor for the PTS1 receptor, or PEX5 protein. As such, mutations in PEX13 would be expected to abrogate peroxisomal protein import and result in PBD phenotypes. We report here the structure of the human PEX13 gene, PE X13 spans approximately 11 kb on chromosome 2 and contains four exons, one more than previously thought. The corrected PEX13 cDNA is predicted to enco de a protein product with a molecular mass of 44,312 Da, We examined the ab ility of PEX13 expression to rescue the peroxisomal protein import defects of fibroblast cells representing all known PBD complementation groups, No c omplementation was observed, suggesting that this gene is not mutated in an y set of existing patients. However, given that complementation group assig nments have been determined for only a subset of PBD patients, it is possib le that PEX13-deficient patients may exist at a low frequency within our ex isting PBD patient population or within ethnic groups underrepresented in o ur patient pool. (C) 1998 Academic Press.