Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Muthaffar, Osama Y., Jan, Mohammed M. S., Alyazidi, Anas S., Alotibi, Taif K., Alsulami, Eman A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785110706989826048
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
work_keys_str_mv AT muthaffarosamay insightintogeneticmutationsofszt2isitasyndrome
AT janmohammedms insightintogeneticmutationsofszt2isitasyndrome
AT alyazidianass insightintogeneticmutationsofszt2isitasyndrome
AT alotibitaifk insightintogeneticmutationsofszt2isitasyndrome
AT alsulamiemana insightintogeneticmutationsofszt2isitasyndrome