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Developmental and epileptic encephalopathy 82 (DEE82) with novel compound heterozygous mutations of GOT2 gene

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dc.contributor.authorTÜRKDOĞAN, DİLŞAD
dc.contributor.authorsÇapan Ö. Y., TÜRKDOĞAN D., Atalay S., Çağlayan H. S.
dc.date.accessioned2023-11-27T08:59:06Z
dc.date.available2023-11-27T08:59:06Z
dc.date.issued2023-01-01
dc.description.abstractPurpose: Developmental and Epileptic Encephalopathies (DEEs) are rare neurological disorders characterized by early-onset medically resistant epileptic seizures, structural brain malformations, and severe developmental delays. These disorders can arise from mutations in genes involved in vital metabolic pathways, including those within the brain. Recent studies have implicated defects in the mitochondrial malate aspartate shuttle (MAS) as potential contributors to the clinical manifestation of infantile epileptic encephalopathy. Although rare, mutations in MDH1, MDH2, AGC1, or GOT2 genes have been reported in patients exhibiting neurological symptoms such as global developmental delay, epilepsy, and progressive microcephaly. Method: In this study, we employed exome data analysis of a patient diagnosed with DEE, focusing on the screening of 1896 epilepsy-related genes listed in the HPO and ClinVar databases. Sanger sequencing was subsequently conducted to validate and assess the inheritance pattern of the identified variants within the family. The evolutionary conservation scores of the mutated residues were evaluated using the ConSurf Database. Furthermore, the impacts of the causative variations on protein stability were analyzed through I-Mutant and MuPro bioinformatic tools. Structural comparisons between wild-type and mutant proteins were performed using PyMOL, and the physicochemical effects of the mutations were assessed using Project Hope. Results: Exome data analysis unveiled the presence of novel compound heterozygous mutations in the GOT2 gene coding for mitochondrial glutamate aspartate transaminase. Sanger sequencing confirmed the paternal inheritance of the p.Asp257Asn mutation and the maternal inheritance of the p.Arg262Cys mutation. The affected individual exhibited plasma metabolic disturbances, including hyperhomocysteinemia, hyperlactatemia, and reduced levels of methionine and arginine. Detailed bioinformatic analysis indicated that the mutations were located within evolutionarily conserved domains of the enzyme, resulting in disruptions to protein stability and structure. Conclusion: Herein, we describe a case with DEE82 (MIM: # 618721) with pathologic novel biallelic mutations in the GOT2 gene. Early genetic diagnosis of metabolic epilepsies is crucial for long-term neurodevelopmental improvements and seizure control as targeted treatments can be administered based on the affected metabolic pathways.
dc.identifier.citationÇapan Ö. Y., TÜRKDOĞAN D., Atalay S., Çağlayan H. S., "Developmental and epileptic encephalopathy 82 (DEE82) with novel compound heterozygous mutations of GOT2 gene", Seizure, 2023
dc.identifier.doi10.1016/j.seizure.2023.11.003
dc.identifier.issn1059-1311
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85176952526&origin=inward
dc.identifier.urihttps://hdl.handle.net/11424/295161
dc.language.isoeng
dc.relation.ispartofSeizure
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectTıp
dc.subjectDahili Tıp Bilimleri
dc.subjectNöroloji
dc.subjectSağlık Bilimleri
dc.subjectMedicine
dc.subjectInternal Medicine Sciences
dc.subjectNeurology
dc.subjectHealth Sciences
dc.subjectKlinik Tıp (MED)
dc.subjectKlinik Tıp
dc.subjectKLİNİK NÖROLOJİ
dc.subjectClinical Medicine (MED)
dc.subjectCLINICAL MEDICINE
dc.subjectCLINICAL NEUROLOGY
dc.subjectYaşam Bilimleri
dc.subjectNöroloji (klinik)
dc.subjectLife Sciences
dc.subjectNeurology (clinical)
dc.subjectAspartate aminotransferase
dc.subjectDevelopmental and epileptic encephalopathies
dc.subjectGOT2 enzyme
dc.subjectInborn error of metabolism
dc.subjectMalate-aspartate shuttle
dc.subjectMetabolic epilepsy
dc.subjectVitamin B6 therapy
dc.subjectWhole exome sequencing
dc.titleDevelopmental and epileptic encephalopathy 82 (DEE82) with novel compound heterozygous mutations of GOT2 gene
dc.typearticle
dspace.entity.typePublication
local.avesis.id1cf28a45-5e3a-4a35-a07b-d8446c986c29
local.indexed.atPUBMED
local.indexed.atSCOPUS
relation.isAuthorOfPublication0a1599c4-48ff-4aa9-b689-3927c986a650
relation.isAuthorOfPublication.latestForDiscovery0a1599c4-48ff-4aa9-b689-3927c986a650

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