Novel PEX1 mutations and genotype=phenotype correlations in Australasian peroxisome biogenesis disorder patients

Maxwell, MA, Allen, T, Solly, PB, Svingen, T, Paton, BC and Crane, DI (2002) Novel PEX1 mutations and genotype=phenotype correlations in Australasian peroxisome biogenesis disorder patients. Human Mutation, 20 5: 342-351. doi:10.1002/humu.10128


Author Maxwell, MA
Allen, T
Solly, PB
Svingen, T
Paton, BC
Crane, DI
Title Novel PEX1 mutations and genotype=phenotype correlations in Australasian peroxisome biogenesis disorder patients
Journal name Human Mutation   Check publisher's open access policy
ISSN 1059-7794
Publication date 2002-11
Sub-type Article (original research)
DOI 10.1002/humu.10128
Volume 20
Issue 5
Start page 342
End page 351
Total pages 10
Place of publication United States
Publisher John Wiley & Sons, Inc.
Language eng
Abstract The peroxisome biogenesis disorders (PBDs) are a group of neuronal migration/neurodegenerative disorders that arise from defects in PEX genes. A major subgroup of the PBDs includes Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). These three disorders represent a clinical continuum with Zellweger syndrome the most severe. Mutations in the PEX1 gene, which encodes a protein of the AAA ATPase family involved in peroxisome matrix protein import, account for the genetic defect in more than half of the patients in this PBD subgroup. We report here on the results of PEX1 mutation detection in an Australasian cohort of PEX1-deficient PBD patients. This screen has identified five novel mutations, including nonsense mutations in exons 14 and 19 and single nucleotide deletions in exons 5 and 18. Significantly, the allele carrying the exon 18 frameshift mutation is present at moderately high frequency (approx. 10%) in this patient cohort. The fifth mutation is a missense mutation (R798G) that attenuates, but does not abolish PEX1 function. We have evaluated the cellular impact of these novel mutations, along with that of the two most common PEX1 mutations (c.2097-2098insT and G843D), in PBD patients by determining the levels of PEX1 mRNA, PEX1 protein, and peroxisome protein import. The findings are consistent with a close correlation between cellular phenotype, disease severity, and PEX1 genotype
Keyword Infantile Refsum disease
IRD
Mutation detection
Neonatal adrenoleukodystrophy
NALD
Peroxisome biogenesis disorder
PBD
PEX1
Zellweger syndrome
ZS
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 24 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 04 May 2011, 14:19:51 EST by Dr Terje Svingen on behalf of Institute for Molecular Bioscience