DEPDC5 plays a vital role in epilepsy: Genotypic and phenotypic features in cohort and literature

IF 1.9 4区医学 Q3 CLINICAL NEUROLOGY

Epileptic Disorders Pub Date : 2024-05-16 DOI:10.1002/epd2.20223

Chunyu Gu, Xinping Wei, Dandan Yan, Yingzi Cai, Dong Li, Jianbo Shu, Chunquan Cai

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引用次数: 0

Abstract

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.

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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

目的：DEPDC5 在局灶性癫痫中扮演着重要角色。然而，DEPDC5相关局灶性癫痫的基因型与表型之间的相关性具有挑战性和争议性。本研究旨在调查受 DEPDC5 影响的患者的基因型和表型特征：方法：结合美国医学遗传学和基因组学学院以及分子病理学协会（ACMG/AMP）公布的标准，在 479 例局灶性癫痫患者中进行基因检测，以确定 DEPDC5 的致病/可能致病变异。此外，还进行了文献综述，以探讨与DEPDC5相关的局灶性癫痫的基因型-表型相关性和渗透性：结果：发现8名无亲属关系的原发性癫痫患者携带不同的DEPDC5致病/可能致病变体，DEPDC5相关局灶性癫痫的总患病率为1.67%。来自 28 项研究的 65 个变体被纳入我们的综述。结合所报告的病例，空变异所占比例大于错义变异，且与不良预后有关（耐药甚至癫痫意外猝死；χ2 = 5.429，p = .020）。而伴有发育迟缓/智力障碍或局灶性皮质发育不良的概率比单纯性癫痫的概率预后更差（χ2 = -，P = .006）。此外，DEPDC5变异的总体渗透率为68.96%（231/335）：该研究扩大了 DEPDC5 的变异谱，证明 DEPDC5 变异在局灶性癫痫中起着重要作用。由于DEPDC5变异具有表型异质性和不完全渗透性的特点，因此尽管没有特定的家族史，也有必要进行基因检测。我们建议采用经 ClinGen 序列变异解释工作组完善的 ACMG/AMP 标准，以保证使用的一致性和分类依据的透明度。此外，我们还向临床医生揭示了一个重要信息，即受 DEPDC5 影响的患者的预后与变异类型和并发症有关。

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

Epileptic Disorders 医学-临床神经学

CiteScore

4.10

自引率

8.70%

发文量

138

审稿时长

6-12 weeks

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.