Baoguang Li, Zhenzhen Qu, Wenjuan Wu, Weiping Wang
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引用次数: 0
Abstract
Mutations in the DEPDC5 gene are inherited in an autosomal dominant manner and can lead to various clinical phenotypes, including focal seizures. While numerous case reports on DEPDC5 mutations exist, functional validation studies remain scarce. We analyzed seven cases of epilepsy or developmental disorders caused by DEPDC5 mutations, summarizing their clinical manifestations and conducting genetic analysis of the mutation sites. The age of onset in the seven patients ranged from 2 months to 4 years. Six mutation sites were identified, including three nonsense mutations: c.1443del (p.C481X), c.2512 C > T (p.R838X), and c.2620 C > T (p.R874X); one missense mutation: c.1140 C > A (p.F380L); and two splice-site mutations: c.2802-13 C > G (splicing) and c.4034-2 A > G (splicing). Among these, c.2512 C > T (p.R838X) and c.2620 C > T (p.R874X) had been previously reported, while the remaining mutations were novel. Minigene experiments confirmed that the c.4034-2 A > G mutation resulted in a slightly truncated protein.Focal seizures were the predominant symptom in six cases. Among the four patients with nonsense mutations, three (Cases 2, 4, and 5) exhibited drug-resistant epilepsy. Four out of seven patients responded effectively to lacosamide treatment. DEPDC5 mutations can cause focal seizures, with truncating mutations associated with more severe symptoms. Lacosamide may offer better therapeutic outcomes. The intronic mutation c.463 + 4 A > G (splicing) led to protein truncation and was determined to be pathogenic.
DEPDC5基因突变以常染色体显性方式遗传,可导致各种临床表型,包括局灶性癫痫发作。虽然存在许多关于DEPDC5突变的病例报告,但功能验证研究仍然很少。我们分析了7例由DEPDC5突变引起的癫痫或发育障碍,总结其临床表现并对突变位点进行遗传分析。7例患者发病年龄从2个月到4岁不等。共鉴定出6个突变位点,包括3个无义突变位点:c.1443del (p.C481X)、c.2512C > T (p.R838X)和C 2620C > T (p.R874X);一个错义突变:c.1140C > A (p.F380L);两个剪接位点突变:C .2802-13 C > G(剪接)和C .4034-2 A > G(剪接)。其中,c.2512C > T (p.R838X)和C 2620C b> T (p.R874X)先前已被报道,而其余的突变是新发现的。Minigene实验证实,c.4034-2 A > G突变导致蛋白质略有截短。局灶性癫痫是6例的主要症状。在4例无义突变患者中,3例(病例2、4和5)表现为耐药癫痫。7名患者中有4名对拉科沙胺治疗有效。DEPDC5突变可引起局灶性癫痫发作,截断突变与更严重的症状相关。拉科沙胺可能提供更好的治疗效果。内含子突变c.463 + 4 A > G(剪接)导致蛋白截断,并被确定为致病性。
期刊介绍:
Neurogenetics publishes findings that contribute to a better understanding of the genetic basis of normal and abnormal function of the nervous system. Neurogenetic disorders are the main focus of the journal. Neurogenetics therefore includes findings in humans and other organisms that help understand neurological disease mechanisms and publishes papers from many different fields such as biophysics, cell biology, human genetics, neuroanatomy, neurochemistry, neurology, neuropathology, neurosurgery and psychiatry.
All papers submitted to Neurogenetics should be of sufficient immediate importance to justify urgent publication. They should present new scientific results. Data merely confirming previously published findings are not acceptable.