PEX3 is the causal gene responsible for peroxisome membrane assembly-defective Zellweger syndrome of complementation group G

Kamran Ghaedi, Masanori Honsho, Nobuyuki Shimozawa, Yasuyuki Suzuki, Naomi Kondo, Yukio Fujiki

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy are autosomal recessive diseases caused by defects in peroxisome assembly, for which 13 genotypes have been identified. Expression of the human peroxin Pex3p cDNA encoding a 373-amino-acid peroxisomal membrane protein morphologically and biochemically restored peroxisome biogenesis, including peroxisomal membrane assembly, in fibroblasts from PBDG-02, a patient with complementation group G (CG-G) ZS. Patient PBDG-02 carried a homozygous, inactivating mutation - a 97-bp deletion of nucleotide residues at positions 942-1038 - resulting in a 32-amino-acid truncation and in a frameshift inducing both a 3-amino-acid substitution and a termination codon. Genomic PCR analysis revealed mutation of T→G at eight bases upstream of the splicing site at the boundary of intron 10 and exon 11 of PEX3 gene, giving rise to a deletion of all of exon 11. When assessed by expression in a pex3 mutant of Chinese hamster ovary cells and the patient's fibroblasts, PBDG-02-derived PEX3 cDNA was found to be defective in peroxisome-restoring activity. These results provide evidence that PEX3 is a novel, pathogenic gene responsible for CG-G PBDs.

Original languageEnglish
Pages (from-to)976-981
Number of pages6
JournalAmerican journal of human genetics
Volume67
Issue number4
DOIs
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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