De novo variants of DEAF1 cause intellectual disability in six Chinese patients
De novo variants of DEAF1 cause intellectual disability in six Chinese patients
复制标题
DEAF1的新生变异导致六名中国患者智力障碍
DOI：
10.1016/j.cca.2021.02.026
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发表时间：
2021-03-22
影响因子：
5
通讯作者：
Yin, Fei
中科院分区：
文献类型：
--
作者：
Chen, Shimeng;Deng, Xiaolu;Yin, Fei
背景：据报道，DEAF1的从头开始杂合变异可导致DEAF1相关的神经发育障碍。本文旨在探讨中国人DEAF1基因新变异者的临床和遗传学特征。方法：我们收集了6例DEAF1基因新变异者。结果：所有患儿均表现为智力残疾(ID)/全球发育迟缓(GDD)。严重的语言障碍突出。行为问题、癫痫发作、睡眠障碍和高痛阈值是常见的特征。据报道，与DEAF1相关的癫痫发作很难治疗或难以治愈。我们队列中的癫痫发作几乎都是可以治疗的。丙戊酸是最常用的药物。发现5个DEAF1基因杂合性错义突变，其中3个(p.W234C、p.L203P、p.H275Q)未见文献报道。结论：ID/GDD患者具有非特异性表型，包括智力障碍、言语障碍、行为异常，尤其是自闭症，应考虑DEAF1基因突变。在我们的研究中，与其他地区的患者相比，东亚人的DEAF1相关癫痫是完全可以治疗的，丙戊酸可以作为首选。扩大了DEAF1相关神经发育障碍的知识和DEAF1从头变异数据库。
Background: It has been reported that de novo heterozygous variants of DEAF1 can cause DEAF1-associated neurodevelopmental disorder. The purpose of this article is to explore the clinical and genetic characteristics of Chinese patients harboring de novo DEAF1 variants.Methods: We assembled a cohort of six unrelated patients with de novo variants in DEAF1. Clinical and genetic features of these patients were summarized.Results: Each child showed intellectual disability (ID)/ global developmental delay (GDD). Severe language impairment was prominent. Behavior problems, seizures, sleep disturbance, and a high pain threshold were common features. DEAF1-related seizures were reported to be difficult to treat or intractable. Seizures in our cohort were almost all treatable. Valproic acid was the most commonly used drug. Five heterozygous missense mutations of DEAF1 gene were identified, three of which (p.W234C, p.L203P, p.H275Q) were not published in literature before.Conclusion: Mutations of DEAF1 gene should be considered in ID/GDD patients with a nonspecific phenotype, comprising intellectual disability, prominent speech delay, abnormal behaviors, especially autism. In our study, DEAF1-related epilepsy is completely treatable in Eastern-Asian individuals when compared to patients in other regions, and valproic acid can be used as a first choice. The knowledge of DEAF1-related neurodevelopmental disorder and the de novo variant database of DEAF1 were expanded.