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Insight into Genetic Mutations of SZT2: Is It a Syndrome?
Background: The seizure threshold 2 (SZT2) gene encodes a protein of unknown function, which is widely expressed, confers a low seizure threshold, and enhances epileptogenesis. It also comprises the KICSTOR protein complex, which inhibits the mTORC1 pathway. A pathogenic variant in the SZT2 gene cou...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525120/ https://www.ncbi.nlm.nih.gov/pubmed/37760843 http://dx.doi.org/10.3390/biomedicines11092402 |
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author | Muthaffar, Osama Y. Jan, Mohammed M. S. Alyazidi, Anas S. Alotibi, Taif K. Alsulami, Eman A. |
author_facet | Muthaffar, Osama Y. Jan, Mohammed M. S. Alyazidi, Anas S. Alotibi, Taif K. Alsulami, Eman A. |
author_sort | Muthaffar, Osama Y. |
collection | PubMed |
description | Background: The seizure threshold 2 (SZT2) gene encodes a protein of unknown function, which is widely expressed, confers a low seizure threshold, and enhances epileptogenesis. It also comprises the KICSTOR protein complex, which inhibits the mTORC1 pathway. A pathogenic variant in the SZT2 gene could result in hyperactive mTORC1 signaling, which can lead to several neurological disorders. Aim of the study: To review every reported case and present two novel cases to expand the current knowledge and understanding of the mutation. Methods: Whole exome sequencing (WES) was used to identify the novel cases and present their clinical and radiological findings. A detailed revision of the literature was conducted to illustrate and compare findings. The clinical, genetical, neuroimaging, and electrophysiological data were extracted. Results: The study included 16 female patients and 13 male patients in addition to the 2 novel male cases. Eighteen patients had heterozygous mutations; others were homozygous. The majority presented with facial dysmorphism (n = 22). Seizures were noted as the predominant hallmark (n = 26). Developmental delay and hypotonia were reported in 27 and 15 patients, respectively. The majority of patients had multifocal epileptiform discharges on the electroencephalogram (EEG) and short and thick corpus callosum on the magnetic resonance imaging (MRI). Conclusion: Several promising features are becoming strongly linked to patients with SZT2 mutations. High variability among the cases was observed. Developmental delay and facial dysmorphism can be investigated as potential hallmarks; aiding clinicians in diagnosing the condition and optimizing management plans. |
format | Online Article Text |
id | pubmed-10525120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105251202023-09-28 Insight into Genetic Mutations of SZT2: Is It a Syndrome? Muthaffar, Osama Y. Jan, Mohammed M. S. Alyazidi, Anas S. Alotibi, Taif K. Alsulami, Eman A. Biomedicines Article Background: The seizure threshold 2 (SZT2) gene encodes a protein of unknown function, which is widely expressed, confers a low seizure threshold, and enhances epileptogenesis. It also comprises the KICSTOR protein complex, which inhibits the mTORC1 pathway. A pathogenic variant in the SZT2 gene could result in hyperactive mTORC1 signaling, which can lead to several neurological disorders. Aim of the study: To review every reported case and present two novel cases to expand the current knowledge and understanding of the mutation. Methods: Whole exome sequencing (WES) was used to identify the novel cases and present their clinical and radiological findings. A detailed revision of the literature was conducted to illustrate and compare findings. The clinical, genetical, neuroimaging, and electrophysiological data were extracted. Results: The study included 16 female patients and 13 male patients in addition to the 2 novel male cases. Eighteen patients had heterozygous mutations; others were homozygous. The majority presented with facial dysmorphism (n = 22). Seizures were noted as the predominant hallmark (n = 26). Developmental delay and hypotonia were reported in 27 and 15 patients, respectively. The majority of patients had multifocal epileptiform discharges on the electroencephalogram (EEG) and short and thick corpus callosum on the magnetic resonance imaging (MRI). Conclusion: Several promising features are becoming strongly linked to patients with SZT2 mutations. High variability among the cases was observed. Developmental delay and facial dysmorphism can be investigated as potential hallmarks; aiding clinicians in diagnosing the condition and optimizing management plans. MDPI 2023-08-28 /pmc/articles/PMC10525120/ /pubmed/37760843 http://dx.doi.org/10.3390/biomedicines11092402 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Muthaffar, Osama Y. Jan, Mohammed M. S. Alyazidi, Anas S. Alotibi, Taif K. Alsulami, Eman A. Insight into Genetic Mutations of SZT2: Is It a Syndrome? |
title | Insight into Genetic Mutations of SZT2: Is It a Syndrome? |
title_full | Insight into Genetic Mutations of SZT2: Is It a Syndrome? |
title_fullStr | Insight into Genetic Mutations of SZT2: Is It a Syndrome? |
title_full_unstemmed | Insight into Genetic Mutations of SZT2: Is It a Syndrome? |
title_short | Insight into Genetic Mutations of SZT2: Is It a Syndrome? |
title_sort | insight into genetic mutations of szt2: is it a syndrome? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525120/ https://www.ncbi.nlm.nih.gov/pubmed/37760843 http://dx.doi.org/10.3390/biomedicines11092402 |
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