De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy.

IF 1.6 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2025-06-01 DOI:10.1002/mgg3.70114

Bingbing Zhang, Xiaohua Li, Xiao Qian, Jihong Tang

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引用次数: 0

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.

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与发育迟缓和局灶性癫痫相关的GBX1基因从头变异。

背景：原肠胚脑同源盒（Gbx）家族，包括GBX1和GBX2，对后脑发育至关重要，并参与中脑-后脑边界（MHB）的形态发生。虽然GBX1基因在人类神经系统发育中的作用仍有待阐明，但其在人类中的变异此前尚未报道与疾病相关。方法：对睡眠惊恐发作患者进行全面的临床评估，包括脑电图（EEG）、磁共振成像（MRI）和全外显子组测序（WES）基因检测。通过gbx1基因crispants生成斑马鱼模型，以研究鉴定的遗传变异对功能的影响。结果：本例患者经远端脑电图诊断为局灶性癫痫。WES发现了一个新的GBX1基因变异[NM_001098834.3: c.910C>T (p.Gln304*)]。在gbx1基因破坏的斑马鱼幼虫中，观察到眼间区域形态的明显异常。此外，这些幼虫表现出对与癫痫样活动相关的神经生理异常的易感性增加。结论：我们的研究首次确定了GBX1基因变异与局灶性癫痫之间的关联。斑马鱼模型证实了gbx1-Cas9中相关表型的存在。这些发现强调了GBX1基因在神经功能中的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.