Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene

Abstract Background Variations in the WWOX gene have been identified as the leading cause of several central nervous system disorders. However, most previous reports have focused on the description of clinical phenotype, neglecting functional verification. Herein, we presented a case of a patient wi...

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Main Authors: Yang You, Wenjuan Wu, Yakun Du, Jintong Hu, Baoguang Li
Format: Article
Language:English
Published: Wiley 2024-08-01
Series:Molecular Genetics & Genomic Medicine
Subjects:
Online Access:https://doi.org/10.1002/mgg3.2500
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author Yang You
Wenjuan Wu
Yakun Du
Jintong Hu
Baoguang Li
author_facet Yang You
Wenjuan Wu
Yakun Du
Jintong Hu
Baoguang Li
author_sort Yang You
collection DOAJ
description Abstract Background Variations in the WWOX gene have been identified as the leading cause of several central nervous system disorders. However, most previous reports have focused on the description of clinical phenotype, neglecting functional verification. Herein, we presented a case of a patient with developmental epileptic encephalopathy (DEE) caused by WWOX gene variation. Case Presentation Our patient was a 13‐month‐old girl with abnormal facial features, including facial hypotonia, arched eyebrows, a broad nose, and a depressed nasal bridge. She also had sparse and yellow hair, a low anterior hairline, and a short neck. Before the age of 8 months, she was suffering from mild seizures. Her developmental delay gradually worsened, and she suffered infantile spasms. After treatment with vigabatrin, seizures subsided. WWOX gene homozygous variation c.172+1G>C was identified using whole exome sequencing. Further minigene assay confirmed that the variation site affected splicing, causing protein truncation and affecting its function. Conclusion Clinical phenotype and minigene results suggest that WWOX gene homozygous variation c.172+1G>C can cause severe DEE. We also concluded that vigabatrin can effectively treat seizures.
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spelling doaj-art-11f8c2cee0fc4677857d93ebe01e9a7e2025-08-20T02:36:09ZengWileyMolecular Genetics & Genomic Medicine2324-92692024-08-01128n/an/a10.1002/mgg3.2500Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX geneYang You0Wenjuan Wu1Yakun Du2Jintong Hu3Baoguang Li4Department of Imaging The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei P.R. ChinaDepartment of Neurology Hebei Medical University, Hebei Children's Hospital Shijiazhuang Hebei P.R. ChinaDepartment of Neurology Hebei Medical University, Hebei Children's Hospital Shijiazhuang Hebei P.R. ChinaDepartment of Neurology Hebei Medical University, Hebei Children's Hospital Shijiazhuang Hebei P.R. ChinaDepartment of Neurology Hebei Medical University, Hebei Children's Hospital Shijiazhuang Hebei P.R. ChinaAbstract Background Variations in the WWOX gene have been identified as the leading cause of several central nervous system disorders. However, most previous reports have focused on the description of clinical phenotype, neglecting functional verification. Herein, we presented a case of a patient with developmental epileptic encephalopathy (DEE) caused by WWOX gene variation. Case Presentation Our patient was a 13‐month‐old girl with abnormal facial features, including facial hypotonia, arched eyebrows, a broad nose, and a depressed nasal bridge. She also had sparse and yellow hair, a low anterior hairline, and a short neck. Before the age of 8 months, she was suffering from mild seizures. Her developmental delay gradually worsened, and she suffered infantile spasms. After treatment with vigabatrin, seizures subsided. WWOX gene homozygous variation c.172+1G>C was identified using whole exome sequencing. Further minigene assay confirmed that the variation site affected splicing, causing protein truncation and affecting its function. Conclusion Clinical phenotype and minigene results suggest that WWOX gene homozygous variation c.172+1G>C can cause severe DEE. We also concluded that vigabatrin can effectively treat seizures.https://doi.org/10.1002/mgg3.2500developmental epileptic encephalopathyepilepsyWWOX
spellingShingle Yang You
Wenjuan Wu
Yakun Du
Jintong Hu
Baoguang Li
Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene
Molecular Genetics & Genomic Medicine
developmental epileptic encephalopathy
epilepsy
WWOX
title Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene
title_full Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene
title_fullStr Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene
title_full_unstemmed Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene
title_short Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene
title_sort developmental epileptic encephalopathy caused by homozygosity of a c 172 1g c variant in the wwox gene
topic developmental epileptic encephalopathy
epilepsy
WWOX
url https://doi.org/10.1002/mgg3.2500
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AT wenjuanwu developmentalepilepticencephalopathycausedbyhomozygosityofac1721gcvariantinthewwoxgene
AT yakundu developmentalepilepticencephalopathycausedbyhomozygosityofac1721gcvariantinthewwoxgene
AT jintonghu developmentalepilepticencephalopathycausedbyhomozygosityofac1721gcvariantinthewwoxgene
AT baoguangli developmentalepilepticencephalopathycausedbyhomozygosityofac1721gcvariantinthewwoxgene