Document Detail

Mutations in novel peroxin gene PEX26 that cause peroxisome-biogenesis disorders of complementation group 8 provide a genotype-phenotype correlation.
MedLine Citation:
PMID:  12851857     Owner:  NLM     Status:  MEDLINE    
The human disorders of peroxisome biogenesis (PBDs) are subdivided into 12 complementation groups (CGs). CG8 is one of the more common of these and is associated with varying phenotypes, ranging from the most severe, Zellweger syndrome (ZS), to the milder neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD). PEX26, encoding the 305-amino-acid membrane peroxin, has been shown to be deficient in CG8. We studied the PEX26 genotype in fibroblasts of eight CG8 patients--four with the ZS phenotype, two with NALD, and two with IRD. Catalase was mostly cytosolic in all these cell lines, but import of the proteins that contained PTS1, the SKL peroxisome targeting sequence, was normal. Expression of PEX26 reestablished peroxisomes in all eight cell lines, confirming that PEX26 defects are pathogenic in CG8 patients. When cells were cultured at 30 degrees C, catalase import was restored in the cell lines from patients with the NALD and IRD phenotypes, but to a much lesser extent in those with the ZS phenotype, indicating that temperature sensitivity varied inversely with the severity of the clinical phenotype. Several types of mutations were identified, including homozygous G89R mutations in two patients with ZS. Expression of these PEX26 mutations in pex26 Chinese hamster ovary cells resulted in cell phenotypes similar to those in the human cell lines. These findings confirm that the degree of temperature sensitivity in pex26 cell lines is predictive of the clinical phenotype in patients with PEX26 deficiency.
Naomi Matsumoto; Shigehiko Tamura; Satomi Furuki; Non Miyata; Ann Moser; Nobuyuki Shimozawa; Hugo W Moser; Yasuyuki Suzuki; Naomi Kondo; Yukio Fujiki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-07-08
Journal Detail:
Title:  American journal of human genetics     Volume:  73     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-07-17     Completed Date:  2003-09-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  233-46     Citation Subset:  IM    
Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka, Japan.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AB014598;  AB089678;  AB103104;  AB103105;  AB103106;  AB103107;  AB103108;  AB103109;  AB103110
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MeSH Terms
Amino Acid Sequence
CHO Cells
Catalase / metabolism
Cell Line
DNA / genetics
DNA Mutational Analysis
Gene Expression
Genetic Complementation Test
Membrane Proteins / deficiency,  genetics*
Molecular Sequence Data
Peroxisomal Disorders / classification,  genetics*,  metabolism
RNA, Messenger / genetics,  metabolism
Receptors, Cytoplasmic and Nuclear / metabolism
Sequence Homology, Amino Acid
Tissue Distribution
Zellweger Syndrome / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Membrane Proteins; 0/PEX26 protein, human; 0/RNA, Messenger; 0/Receptors, Cytoplasmic and Nuclear; 0/peroxisome-targeting signal 1 receptor; 9007-49-2/DNA; EC

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