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.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- DEE71 :
-
Developmental and epileptic encephalopathy type 71;
- OMIM :
-
Online Mendelian inheritance in man;
- ACMG :
-
American College of Medical Genetics;
- WES :
-
Whole-exome sequencing;
- MAF :
-
Minor allele frequency;
- MRI :
-
Brain magnetic resonance imaging
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Acknowledgements
We are very thankful to the patient’s family members for collaborating in this study, and also thankful to the staff of the DeNA laboratory, in Tehran, Iran, for helping us in this study.
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A.B. and M.G. designed the basic concept of the research. A.R.T. carried out sample collection and clinical examinations. A.B., M.A.GH., and S.M.K. coordinated the genetic tests, the raw data and bioinformatics analysis. A.B. and M.A.GH. wrote the manuscript with valuable scientific commentary and input from all authors. All authors read and approved the final manuscript.
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Ethics Committee of Children's Medical Center Hospital, Tehran, Iran approved the study and was conducted according to the ethical principle of the Declaration of Helsinki.
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We obtained written informed consent from all family participants. Specifically, the parents of the minor patient (5 years old) provided signed informed consent forms for their participation in clinical and genetic research.
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Bazgir, A., Agha Gholizadeh, M., Kahani, S.M. et al. Identification of a Novel Homozygous GLS Gene Variant Associated with Developmental and Epileptic Encephalopathy (DEE) Type 71. Neurogenetics (2024). https://doi.org/10.1007/s10048-024-00753-z
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DOI: https://doi.org/10.1007/s10048-024-00753-z