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

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI:10.1002/mgg3.2500

Yang You, Wenjuan Wu, Yakun Du, Jintong Hu, Baoguang Li

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引用次数: 0

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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WWOX基因中c.172+1G>C变异的同源性导致的发育性癫痫脑病。

背景：WWOX 基因变异已被确定为多种中枢神经系统疾病的主要病因。然而，以往的报道大多侧重于临床表型的描述，而忽略了功能验证。在此，我们介绍了一例由 WWOX 基因变异引起的发育性癫痫性脑病（DEE）患者：我们的患者是一名 13 个月大的女孩，面部特征异常，包括面部肌张力低下、弯眉、宽鼻和鼻梁凹陷。她的头发稀疏且呈黄色，前发际线较低，脖子较短。在 8 个月大之前，她曾有过轻微的癫痫发作。她的发育迟缓逐渐恶化，并患有婴儿痉挛症。在接受维加溴铵治疗后，癫痫发作有所缓解。通过全外显子组测序确定了WWOX基因同源变异c.172+1G>C。进一步的迷你基因检测证实，该变异位点影响了剪接，导致蛋白质截短并影响其功能：临床表型和迷你基因结果表明，WWOX 基因同源变异 c.172+1G>C 可导致严重的 DEE。我们还得出结论，维加巴特林能有效治疗癫痫发作。

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.