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Identification of a Novel Homozygous Gls Gene Variant Associated With Developmental and Epileptic Encephalopathy (Dee) Type 71 Publisher



Bazgir A1, 2 ; Agha Gholizadeh M1, 2 ; Kahani SM1, 2 ; Tavasoli AR4, 5 ; Garshasbi M1, 3
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  2. 2. PardisGene Company, Tehran, Iran
  3. 3. Department of Medical Genetics, DeNA Laboratory, Tehran, Iran
  4. 4. Division of Pediatric Neurology, Myelin Disorders Clinic, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Neurology Division, Barrow Neurological Institute, Phoenix Children’s Hospital, Phoenix, AZ, United States

Source: Neurogenetics Published:2024


Abstract

Developmental and epileptic encephalopathy (DEEs) (OMIM#618,328) is characterized by seizures, hypotonia, and brain abnormalities, often arising from mutations in genes crucial for brain function. Among these genes, GLS stands out due to its vital role in the central nervous system (CNS), with homozygous variants potentially causing DEE type 71. Using Whole Exome Sequencing (WES) on a patient exhibiting symptoms of epileptic encephalopathy, we identified a novel homozygous variant, NM_014905.5:c.1849G > T; p.(Asp617Tyr), in the GLS gene. The 5-year-old patient, born to consanguineous parents, presented with developmental delay, encephalopathy, frequent seizures, and hypotonia. Sanger sequencing further validated the GLS gene variant in both the patient and his family. Furthermore, our bioinformatics analysis indicated that this missense variant could lead to alteration of splicing, resulting in the activation of a cryptic donor site and potentially causing loss of protein function. Our finding highlights the pathogenic significance of the GLS gene, particularly in the context of brain disorders, specifically DEE71. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
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