De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy
ABSTRACT Background The gastrulation brain homeobox (Gbx) family, including GBX1 and GBX2, is crucial for hindbrain development and contributes to the morphogenesis of the midbrain–hindbrain boundary (MHB). While the role of the GBX1 gene in the development of the human nervous system remains to be...
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Wiley
2025-06-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.70114 |
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| author | Bingbing Zhang Xiaohua Li Xiao Qian Jihong Tang |
| author_facet | Bingbing Zhang Xiaohua Li Xiao Qian Jihong Tang |
| author_sort | Bingbing Zhang |
| collection | DOAJ |
| description | ABSTRACT Background The gastrulation brain homeobox (Gbx) family, including GBX1 and GBX2, is crucial for hindbrain development and contributes to the morphogenesis of the midbrain–hindbrain boundary (MHB). While the role of the GBX1 gene in the development of the human nervous system remains to be elucidated, its variant in humans has not previously been reported to be associated with disease. Methods The patient presenting with sleep panic attacks underwent comprehensive clinical assessments, including electroencephalograph (EEG), magnetic resonance imaging (MRI), and genetic testing through whole exome sequencing (WES). Zebrafish models were generated through gbx1 gene crispants to investigate the functional impact of identified genetic variants. Results The patient in our study was diagnosed with focal epilepsy through long‐range EEG. WES revealed a de novo GBX1 gene variant [NM_001098834.3: c.910C>T (p.Gln304*)]. In zebrafish larvae with gbx1 gene disruption, significant abnormalities were observed in the morphology of the interocular area. Furthermore, these larvae exhibited an increased susceptibility to neurophysiological abnormalities associated with epileptiform activity. Conclusion Our study is the first to identify an association between the GBX1 gene variant and focal epilepsy. The zebrafish models confirmed the presence of related phenotypes in the gbx1‐Cas9. These findings underscore the significance of the GBX1 gene in neurological function. |
| format | Article |
| id | doaj-art-190be0d17ee947df80f886a1f22df14c |
| institution | DOAJ |
| issn | 2324-9269 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj-art-190be0d17ee947df80f886a1f22df14c2025-08-20T03:23:56ZengWileyMolecular Genetics & Genomic Medicine2324-92692025-06-01136n/an/a10.1002/mgg3.70114De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal EpilepsyBingbing Zhang0Xiaohua Li1Xiao Qian2Jihong Tang3Children's Hospital of Soochow University Jiangsu Province ChinaThe First People's Hospital of Lianyungang Jiangsu Province ChinaCipher Gene LLC Beijing ChinaChildren's Hospital of Soochow University Jiangsu Province ChinaABSTRACT Background The gastrulation brain homeobox (Gbx) family, including GBX1 and GBX2, is crucial for hindbrain development and contributes to the morphogenesis of the midbrain–hindbrain boundary (MHB). While the role of the GBX1 gene in the development of the human nervous system remains to be elucidated, its variant in humans has not previously been reported to be associated with disease. Methods The patient presenting with sleep panic attacks underwent comprehensive clinical assessments, including electroencephalograph (EEG), magnetic resonance imaging (MRI), and genetic testing through whole exome sequencing (WES). Zebrafish models were generated through gbx1 gene crispants to investigate the functional impact of identified genetic variants. Results The patient in our study was diagnosed with focal epilepsy through long‐range EEG. WES revealed a de novo GBX1 gene variant [NM_001098834.3: c.910C>T (p.Gln304*)]. In zebrafish larvae with gbx1 gene disruption, significant abnormalities were observed in the morphology of the interocular area. Furthermore, these larvae exhibited an increased susceptibility to neurophysiological abnormalities associated with epileptiform activity. Conclusion Our study is the first to identify an association between the GBX1 gene variant and focal epilepsy. The zebrafish models confirmed the presence of related phenotypes in the gbx1‐Cas9. These findings underscore the significance of the GBX1 gene in neurological function.https://doi.org/10.1002/mgg3.70114developmental delayfocal epilepsyGBX1whole exome sequencing |
| spellingShingle | Bingbing Zhang Xiaohua Li Xiao Qian Jihong Tang De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy Molecular Genetics & Genomic Medicine developmental delay focal epilepsy GBX1 whole exome sequencing |
| title | De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy |
| title_full | De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy |
| title_fullStr | De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy |
| title_full_unstemmed | De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy |
| title_short | De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy |
| title_sort | de novo variant in gbx1 gene associated with developmental delay and focal epilepsy |
| topic | developmental delay focal epilepsy GBX1 whole exome sequencing |
| url | https://doi.org/10.1002/mgg3.70114 |
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