{"title":"DEPDC5 在癫痫中发挥着重要作用：队列和文献中的基因型和表型特征","authors":"Chunyu Gu, Xinping Wei, Dandan Yan, Yingzi Cai, Dong Li, Jianbo Shu, Chunquan Cai","doi":"10.1002/epd2.20223","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p><i>DEPDC5</i> emerges to play a vital role in focal epilepsy. However, genotype–phenotype correlation in <i>DEPDC5</i>-related focal epilepsies is challenging and controversial. In this study, we aim to investigate the genotypic and phenotypic features in <i>DEPDC5</i>-affected patients.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Genetic testing combined with criteria published by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP), was used to identify pathogenic/likely pathogenic variants in <i>DEPDC5</i> among the cohort of 479 patients with focal epilepsy. Besides, the literature review was performed to explore the genotype–phenotype correlation and the penetrance in <i>DEPDC5</i>-related focal epilepsies.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Eight unrelated probands were revealed to carry different pathogenic/likely pathogenic variants in <i>DEPDC5</i> and the total prevalence of <i>DEPDC5</i>-related focal epilepsy was 1.67% in the cohort. Sixty-five variants from 28 studies were included in our review. Combined with the cases reported, null variants accounted for a larger proportion than missense variants and were related to unfavorable prognosis (drug resistance or even sudden unexpected death in epilepsy; <i>χ</i><sup><i>2</i></sup> = 5.429, <i>p</i> = .020). And, the prognosis of probands with developmental delay/intellectual disability or focal cortical dysplasia was worse than that of probands with simple epilepsy (<i>χ</i><sup><i>2</i></sup> = −, <i>p</i> = .006). Besides, the overall penetrance of variants in <i>DEPDC5</i> was 68.96% (231/335).</p>\n </section>\n \n <section>\n \n <h3> Significance</h3>\n \n <p>The study expands the variant spectrum of <i>DEPDC5</i> and proves that the <i>DEPDC5</i> variant plays a significant role in focal epilepsy. Due to the characteristics of phenotypic heterogeneity and incomplete penetrance, genetic testing is necessary despite no specific family history. And we propose to adopt the ACMG/AMP criteria refined by ClinGen Sequence Variant Interpretation Working Group, for consistency in usage and transparency in classification rationale. Moreover, we reveal an important message to clinicians that the prognosis of <i>DEPDC5</i>-affected patients is related to the variant type and complications.</p>\n </section>\n </div>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"DEPDC5 plays a vital role in epilepsy: Genotypic and phenotypic features in cohort and literature\",\"authors\":\"Chunyu Gu, Xinping Wei, Dandan Yan, Yingzi Cai, Dong Li, Jianbo Shu, Chunquan Cai\",\"doi\":\"10.1002/epd2.20223\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p><i>DEPDC5</i> emerges to play a vital role in focal epilepsy. However, genotype–phenotype correlation in <i>DEPDC5</i>-related focal epilepsies is challenging and controversial. In this study, we aim to investigate the genotypic and phenotypic features in <i>DEPDC5</i>-affected patients.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Genetic testing combined with criteria published by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP), was used to identify pathogenic/likely pathogenic variants in <i>DEPDC5</i> among the cohort of 479 patients with focal epilepsy. Besides, the literature review was performed to explore the genotype–phenotype correlation and the penetrance in <i>DEPDC5</i>-related focal epilepsies.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Eight unrelated probands were revealed to carry different pathogenic/likely pathogenic variants in <i>DEPDC5</i> and the total prevalence of <i>DEPDC5</i>-related focal epilepsy was 1.67% in the cohort. Sixty-five variants from 28 studies were included in our review. Combined with the cases reported, null variants accounted for a larger proportion than missense variants and were related to unfavorable prognosis (drug resistance or even sudden unexpected death in epilepsy; <i>χ</i><sup><i>2</i></sup> = 5.429, <i>p</i> = .020). And, the prognosis of probands with developmental delay/intellectual disability or focal cortical dysplasia was worse than that of probands with simple epilepsy (<i>χ</i><sup><i>2</i></sup> = −, <i>p</i> = .006). Besides, the overall penetrance of variants in <i>DEPDC5</i> was 68.96% (231/335).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Significance</h3>\\n \\n <p>The study expands the variant spectrum of <i>DEPDC5</i> and proves that the <i>DEPDC5</i> variant plays a significant role in focal epilepsy. Due to the characteristics of phenotypic heterogeneity and incomplete penetrance, genetic testing is necessary despite no specific family history. And we propose to adopt the ACMG/AMP criteria refined by ClinGen Sequence Variant Interpretation Working Group, for consistency in usage and transparency in classification rationale. Moreover, we reveal an important message to clinicians that the prognosis of <i>DEPDC5</i>-affected patients is related to the variant type and complications.</p>\\n </section>\\n </div>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2024-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/epd2.20223\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/epd2.20223","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
DEPDC5 plays a vital role in epilepsy: Genotypic and phenotypic features in cohort and literature
Objective
DEPDC5 emerges to play a vital role in focal epilepsy. However, genotype–phenotype correlation in DEPDC5-related focal epilepsies is challenging and controversial. In this study, we aim to investigate the genotypic and phenotypic features in DEPDC5-affected patients.
Methods
Genetic testing combined with criteria published by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP), was used to identify pathogenic/likely pathogenic variants in DEPDC5 among the cohort of 479 patients with focal epilepsy. Besides, the literature review was performed to explore the genotype–phenotype correlation and the penetrance in DEPDC5-related focal epilepsies.
Results
Eight unrelated probands were revealed to carry different pathogenic/likely pathogenic variants in DEPDC5 and the total prevalence of DEPDC5-related focal epilepsy was 1.67% in the cohort. Sixty-five variants from 28 studies were included in our review. Combined with the cases reported, null variants accounted for a larger proportion than missense variants and were related to unfavorable prognosis (drug resistance or even sudden unexpected death in epilepsy; χ2 = 5.429, p = .020). And, the prognosis of probands with developmental delay/intellectual disability or focal cortical dysplasia was worse than that of probands with simple epilepsy (χ2 = −, p = .006). Besides, the overall penetrance of variants in DEPDC5 was 68.96% (231/335).
Significance
The study expands the variant spectrum of DEPDC5 and proves that the DEPDC5 variant plays a significant role in focal epilepsy. Due to the characteristics of phenotypic heterogeneity and incomplete penetrance, genetic testing is necessary despite no specific family history. And we propose to adopt the ACMG/AMP criteria refined by ClinGen Sequence Variant Interpretation Working Group, for consistency in usage and transparency in classification rationale. Moreover, we reveal an important message to clinicians that the prognosis of DEPDC5-affected patients is related to the variant type and complications.
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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