Galloway-mowat syndrome 3 (GAMOS3): a novel disease-causing variant in OSGEP gene and expansion of the clinical spectrum.

Autor: Yari A; Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran., Vafaeie F; Student Research Committee and Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran., Karam ZM; Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran., Hosseini M; Department of Pediatrics, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran. mahyahosseini@bums.ac.ir., Miri-Moghaddam E; Department of Molecular Medicine, Faculty of Medicine and Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran. moghaddam4@yahoo.com.
Jazyk: angličtina
Zdroj: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology [Neurol Sci] 2024 Dec 11. Date of Electronic Publication: 2024 Dec 11.
DOI: 10.1007/s10072-024-07892-z
Abstrakt: Introduction: Galloway-Mowat syndrome type 3 (GAMOS3) is a rare genetic disorder with renal and neurological complications caused by pathogenic variants in the OSGEP gene. Here, we report the molecular basis and clinical features in an Iranian family.
Methods: Our proband, a 10-month-old female patient, presented with microcephaly, global developmental delay, lower limb spasticity, facial dysmorphisms, and renal tubulopathy. Brain magnetic resonance imaging (MRI), electroencephalography (EEG), and laboratory tests were performed to evaluate the clinical features. WES, Sanger sequencing, computational variant analysis, and gene expression analysis were conducted to identify, validate, and evaluate the genetic cause. Additionally, I-TASSER, HADDOCK, and GROMACS tools were utilized for protein modeling, computational docking, and molecular dynamics simulation (MDS), respectively.
Results: Blood and urine tests revealed proteinuria, hypercalciuria, and hypoalbuminemia. Brain MRI detected craniosynostosis, global parenchymal atrophy, and dysgenesis of the corpus callosum. Exome sequencing identified a previously unreported homozygous variant (NM_017807.4, c.689 G > T/p.C230F) in OSGEP, demonstrating co-segregation with the condition in the family. This missense variant did not significantly change the mRNA transcription. In-silico experiments predicted that this variant would likely alter the protein's structure and impair its normal functioning. Molecular docking results indicated that this variant significantly affects the protein interactions between OSGEP and LAGE3 proteins. Furthermore, MDS findings demonstrated that the p.C230F variant induced a conformational change in the mutant structure, potentially modifying its flexibility and stability.
Conclusion: Identification of this variant contributes to expanding the OSGEP gene variant database, establishing a solid scientific foundation for precise clinical diagnosis and treatment.
Competing Interests: Declarations. Ethics approval: This study adhered to the principles outlined in the Declaration of Helsinki for studies involving human participants and all study protocols were approved by the Ethics Committee of Birjand University of Medical Sciences (Ethics code: IR.BUMS.REC.1402.324). Consent to participate: Informed consent documents were obtained from adult participants to participate in the study. For all participants aged under 18, written informed consent was obtained from parents. Consent for publication: Written informed consent was obtained from the parent/legal guardian of the patients for publication of the details of their medical care and any accompanying images presented in thisstudy. Competing interests: The authors declare that they have no competing interests.
(© 2024. Fondazione Società Italiana di Neurologia.)
Databáze: MEDLINE
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