International Journal of Medical Laboratory

en A Novel PEX3 Gene Mutation in a Patient with Zellweger Syndrome ژنتیک/ بیوتکنولوژی Genetics/ Biotechnology گزارش مورد case report <div style="text-align: justify;">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.</div> Bioinformatics analyses, NGS, PEX gene, Zellweger syndrome 12 19 http://ijml.ssu.ac.ir/browse.php?a_code=A-10-475-2&slc_lang=en&sid=1 Seyed Ali Madani Manshadi سیدعلی مدنی منشادی seyedali.m1993@gmail.com No Yazd Science and Technology Park, Yazd, Iran Yazd Science and Technology Park, Yazd, Iran Mojtaba Movahedinia مجتبی موحدی نیا dr.Movahedinia@gmail.com No Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Seyed Mehdi Kalantar سید مهدی کلانتر kalantarseyedmehdi6@gmail.com No Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Negin Yazdian نگین یزدیان Yazdian.n1995@gmail.com No Yazd Science and Technology Park, Yazd, Iran Yazd Science and Technology Park, Yazd, Iran Maliheh Hashemi Nejad ملیحه هاشمی نژاد malihehHashemiNejad@gmail.com No Hasti Medical Genetic Laboratory, Yazd, Iran Hasti Medical Genetic Laboratory, Yazd, Iran Mahya Ebrahimi Nasab محیا ابراهیمی نسب mahyaEbrahimi.1990@gmail.com No Yazd Science and Technology Park, Yazd, Iran Yazd Science and Technology Park, Yazd, Iran Ehsan Zare Mehrjardi احسان زارع مهرجردی ehsan_zare98@yahoo.com Yes Department of Biology, Ashk.C., Islamic Azad University, Ashkezar, Iran Department of Biology, Ashk.C., Islamic Azad University, Ashkezar, Iran