International Journal of Medical Laboratory
Shahid Sadoughi University of Medical Sciences
Tue, Dec 30, 2025
[Archive]
Seyed Ali Madani Manshadi 
, Mojtaba Movahedinia , Seyed Mehdi Kalantar , Negin Yazdian , Maliheh Hashemi Nejad , Mahya Ebrahimi Nasab , Ehsan Zare Mehrjardi *
, Mojtaba Movahedinia , Seyed Mehdi Kalantar , Negin Yazdian , Maliheh Hashemi Nejad , Mahya Ebrahimi Nasab , Ehsan Zare Mehrjardi *
Department of Biology, Ashk.C., Islamic Azad University, Ashkezar, Iran & Medical Biotechnology Research Center, Ashk.C., Islamic Azad University, Ashkezar, Iran
Abstract: (47 Views)
Introduction: Zellweger syndrome (ZS) is a severe peroxisome biogenesis disorder characterized by a deficiency in peroxisomal function due to mutations in various PEX genes.
Case Report: This report describes a 15-year-old male patient diagnosed with ZS, who was found to carry a homozygous variant in the PEX3 gene, specifically p.Glu266Lys. Genetic analysis was performed using next-generation sequencing to identify the mutation, which was subsequently confirmed by Sanger sequencing. The clinical presentation of the patient included developmental delay, hypotonia, and characteristic imaging findings associated with ZS. Bioinformatics analyses were conducted to assess the functional impact of the p.Glu266Lys mutation.
Results: Predictions from various tools indicated that the variant is likely deleterious: SIFT predicted it to be deleterious, PolyPhen-2 classified it as probably damaging, and MutationTaster indicated that it is disease-causing. Structural analyses revealed altered hydrogen bonding and electrostatic interactions that may impair binding with PEX19, a crucial partner for peroxisome biogenesis. Stability predictions showed that the mutation decreases protein stability (ΔΔG = +2.5 kcal/mol), suggesting a destabilizing effect on the PEX3 protein.
Conclusion: This case highlights the significance of PEX3 mutations in the pathogenesis of Zellweger syndrome and underscores the utility of next-generation sequencing combined with Sanger sequencing in uncovering genetic variants that contribute to this disorder. Further investigation into the functional consequences of the p.Glu266Lys variant may provide insights into potential therapeutic strategies and enhance our understanding of the molecular mechanisms underlying peroxisome biogenesis disorders.
Case Report: This report describes a 15-year-old male patient diagnosed with ZS, who was found to carry a homozygous variant in the PEX3 gene, specifically p.Glu266Lys. Genetic analysis was performed using next-generation sequencing to identify the mutation, which was subsequently confirmed by Sanger sequencing. The clinical presentation of the patient included developmental delay, hypotonia, and characteristic imaging findings associated with ZS. Bioinformatics analyses were conducted to assess the functional impact of the p.Glu266Lys mutation.
Results: Predictions from various tools indicated that the variant is likely deleterious: SIFT predicted it to be deleterious, PolyPhen-2 classified it as probably damaging, and MutationTaster indicated that it is disease-causing. Structural analyses revealed altered hydrogen bonding and electrostatic interactions that may impair binding with PEX19, a crucial partner for peroxisome biogenesis. Stability predictions showed that the mutation decreases protein stability (ΔΔG = +2.5 kcal/mol), suggesting a destabilizing effect on the PEX3 protein.
Conclusion: This case highlights the significance of PEX3 mutations in the pathogenesis of Zellweger syndrome and underscores the utility of next-generation sequencing combined with Sanger sequencing in uncovering genetic variants that contribute to this disorder. Further investigation into the functional consequences of the p.Glu266Lys variant may provide insights into potential therapeutic strategies and enhance our understanding of the molecular mechanisms underlying peroxisome biogenesis disorders.
Type of Study: case report |
Subject:
Genetics/ Biotechnology
Received: 2025/08/23 | Accepted: 2025/12/6
Received: 2025/08/23 | Accepted: 2025/12/6
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