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The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6
N Matsumoto1, S Tamura, A Moser
1Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka, Japan.
Insights
Researchers identified the PEX6 gene as the cause of Peroxisomal Biogenesis Disorders (PBDs) in complementation group 6 (CG6). This finding merges CG6 with CG4, reducing human PBD classifications to 12 complementation groups.
Area of Science:
- Genetics
- Cell Biology
- Biochemistry
Background:
- Human genetic peroxisomal biogenesis disorders (PBDs) are a group of severe genetic diseases, previously classified into 13 complementation groups (CGs).
- Eleven peroxin (PEX) genes have been identified as causative for PBDs, but the genetic basis for CG-A and CG6 remained unknown.
Purpose of the Study:
- To identify the pathogenic gene responsible for PBDs in complementation group 6 (CG6).
- To re-evaluate the classification of human PBDs based on newly identified genetic causes.
Main Methods:
- Functional complementation assays using patient-derived fibroblasts.
- Genetic analysis of PBD patients, including compound heterozygote identification.
- Gene expression studies to confirm gene function.
Main Results:
- Evidence indicates that the PEX6 gene, previously associated with CG4, is also impaired in PBD of CG6.
- Expression of the PEX6 gene restored peroxisome assembly in fibroblasts from a CG6 PBD patient.
- The patient was identified as a compound heterozygote for PEX6 gene alleles.
Conclusions:
- The PEX6 gene is the causative gene for PBDs in CG6.
- Complementation group 6 (CG6) can be merged with complementation group 4 (CG4).
- Human PBDs are now classified into 12 complementation groups instead of 13.
Abstract:
Human genetic peroxisomal biogenesis disorders (PBDs), such as Zellweger syndrome, comprise 13 different complementation groups (CGs). Eleven peroxin genes, termed PEXs, responsible for PBDs have been identified, whereas pathogenic genes for PBDs of 2CGs, CG-A (the same CG as CG8 in the United States and Europe) and CG6, remained unidentified. We herein provide several lines of novel evidence indicating that PEX6, the pathogenic gene for CG4, is impaired in PBD of CG6. Expression of PEX6 restored peroxisome assembly in fibroblasts from a CG6 PBD patient. This patient was a compound heterozygote for PEX6 gene alleles. Accordingly, by merging CG6 with CG4, human PBDs are now classified into 12CGs.