The PEX Gene Screen: Molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum

Steven Steinberg, Li Chen, Liumei Wei, Ann Moser, Hugo Moser, Garry Cutting, Nancy Braverman

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Peroxisome biogenesis disorders in the Zellweger syndrome spectrum (PBD-ZSS) are caused by defects in at least 12 PEX genes required for normal organelle assembly. Clinical and biochemical features continue to be used reliably to assign patients to this general disease category. Identification of the precise genetic defect is important, however, to permit carrier testing and early prenatal diagnosis. Molecular analysis is likely to expand the clinical spectrum of PBD and may also provide data relevant to prognosis and future therapeutic intervention. However, the large number of genes involved has thus far impeded rapid mutation identification. In response, we developed the PEX Gene Screen, an algorithm for the systematic screening of exons in the six PEX genes most commonly defective in PBD-ZSS. We used PCR amplification of genomic DNA and sequencing to screen 91 unclassified PBD-ZSS patients for mutations in PEX1, PEX26, PEX6, PEX12, PEX10, and PEX2. A maximum of 14 reactions per patient identified pathological mutations in 79% and both mutant alleles in 54%. Twenty-five novel mutations were identified overall. The proportion of patients with different PEX gene defects correlated with frequencies previously identified by complementation analysis. This systematic, hierarchical approach to mutation identification is therefore a valuable tool to identify rapidly the molecular etiology of suspected PBD-ZSS disorders.

Original languageEnglish (US)
Pages (from-to)252-263
Number of pages12
JournalMolecular genetics and metabolism
Issue number3
StatePublished - Nov 2004


  • Infantile Refsum disease
  • Neonatal adrenoleukodystrophy
  • PEX1
  • PEX10
  • PEX12
  • PEX2
  • PEX26
  • PEX6
  • Peroxisome biogenesis disorder
  • Zellweger syndrome

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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