De novo variants of DEAF1 cause intellectual disability in six Chinese patients

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.