AI Article Synopsis
- Human peroxisome biogenesis disorders (PBDs) are genetic diseases caused by mutations in PEX genes, resulting in severe conditions like Zellweger syndrome and neonatal adrenoleukodystrophy.
- These disorders represent a spectrum of clinical phenotypes, with Zellweger syndrome being the most severe and infantile Refsum's disease the least.
- The human PEX1 gene, linked to these disorders, was identified and shown to correct biogenesis defects in patient cells, indicating its crucial role in PBDs.
Article Abstract
Human peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal-recessive disease caused by mutations in PEX genes that encode peroxins, proteins required for peroxisome biogenesis. These lethal diseases include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum's disease (IRD), three phenotypes now thought to represent a continuum of clinical features that are most severe in ZS, milder in NALD and least severe in IRD2. At least eleven PBD complementation groups have been identified by somatic-cell hybridization analysis compared to the eighteen PEX complementation groups that have been found in yeast. We have cloned the human PEX1 gene encoding a 147-kD member of the AAA protein family (ATPases associated with diverse cellular activities), which is the putative orthologue of Saccharomyces cerevisiae Pex1p (ScPex1p). Human PEX1 has been identified by computer-based 'homology probing' using the ScPex1p sequence to screen databases of expressed sequence tags (dbEST) for human cDNA clones. Expression of PEX1 rescued the cells from the biogenesis defect in human fibroblasts of complementation group 1 (CG1), the largest PBD complementation group. We show that PEX1 is mutated in CG1 patients.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/ng1297-449 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Zellweger spectrum disorder presenting with opsoclonus-myoclonus-ataxia syndrome: a case report on immunotherapy.
Acta Neurol Belg
January 2025
Department of Pediatrics, Neurology Unit, University of Health Sciences, Ankara Etlik City Hospital, Ankara, Turkey.
Introduction: Zellweger spectrum disorder (ZSD) refers to a group of autosomal recessive genetic disorders that affect multiple organ systems and are predominantly caused by pathogenic variants in PEX genes. ZSD present a wide clinical spectrum, ranging from the most severe form, Zellweger syndrome, to the mildest form, Heimler syndrome.
Case Report: A 14-month-old male patient was brought to our clinic with recent-onset ocular tremors and unsteady gait.
Zellweger syndrome; identification of mutations in and gene in Saudi families.
Ann Med
December 2025
Department of Basic Medical Sciences, College of Medicine & Center for Genetics and Inherited Diseases, Taibah University Medina, Medina, Saudi Arabia.
Background: Peroxisome biogenesis disorders (PBD) affect multiple organ systems. It is characterized by neurological dysfunction, hypotonia, ocular anomalies, craniofacial abnormalities, and absence of peroxisomes in fibroblasts. PBDs are associated with mutations in any of fourteen different genes, which are involved in peroxisome biogenesis.
View Article and Find Full Text PDFPEX1 remains functional in peroxisome biogenesis but is rapidly degraded by the proteasome.
bioRxiv
December 2024
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
The PEX1/PEX6 AAA-ATPase is required for the biogenesis and maintenance of peroxisomes. Mutations in and disrupt peroxisomal matrix protein import and are the leading cause of Peroxisome Biogenesis Disorders (PBDs). The most common disease-causing mutation in PEX1 is the PEX1 allele, which results in a reduction of peroxisomal protein import.
View Article and Find Full Text PDFPigmentary retinal dystrophy associated with peroxisome biogenesis disorder-Zellweger syndrome spectrum.
Oxf Med Case Reports
June 2024
Pediatric Ophthalmology, Helen DeVos Children's Hospital, 15 Michigan St NE, Grand Rapids, MI 49503, United States.
Article Synopsis
- Pigmentary retinal dystrophy (PRD) is a genetic disorder that leads to the breakdown of important cells in the retina, potentially causing vision problems.
- A pediatric patient with PRD has been identified with harmful mutations in the PRPH2 and PEX1 genes, resulting in macular swelling and vision loss.
- The case highlights various gene mutations linked to PRD and suggests treatment options including steroid injections and eye drops, while also discussing the management of the condition.
PPARgamma dependent PEX11beta counteracts the suppressive role of SIRT1 on neural differentiation of HESCs.
PLoS One
May 2024
Department of Cellular Biotechnology, Royan Institute for Biotechnology, Cell Science Research Center, ACECR, Isfahan, Iran.
The membrane peroxisomal proteins PEX11, play a crucial role in peroxisome proliferation by regulating elongation, membrane constriction, and fission of pre-existing peroxisomes. In this study, we evaluated the function of PEX11B gene in neural differentiation of human embryonic stem cell (hESC) by inducing shRNAi-mediated knockdown of PEX11B expression. Our results demonstrate that loss of PEX11B expression led to a significant decrease in the expression of peroxisomal-related genes including ACOX1, PMP70, PEX1, and PEX7, as well as neural tube-like structures and neuronal markers.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!