{"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":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9000,"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\":50508,\"journal\":{\"name\":\"Epileptic Disorders\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epileptic Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/epd2.20223\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epileptic Disorders","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/epd2.20223","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","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：
Epileptic Disorders is the leading forum where all experts and medical studentswho wish to improve their understanding of epilepsy and related disorders can share practical experiences surrounding diagnosis and care, natural history, and management of seizures.
Epileptic Disorders is the official E-journal of the International League Against Epilepsy for educational communication. As the journal celebrates its 20th anniversary, it will now be available only as an online version. Its mission is to create educational links between epileptologists and other health professionals in clinical practice and scientists or physicians in research-based institutions. This change is accompanied by an increase in the number of issues per year, from 4 to 6, to ensure regular diffusion of recently published material (high quality Review and Seminar in Epileptology papers; Original Research articles or Case reports of educational value; MultiMedia Teaching Material), to serve the global medical community that cares for those affected by epilepsy.
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