AUTHOR=Xu Lu , Zhou Youfeng , Ren Xiaoyan , Xu Chenlu , Ren Rongna , Yan Xuke , Li Xuelian , Yang Huimin , Xu Xuebin , Guo Xiaotong , Sheng Guoxia , Hua Yi , Yuan Zhefeng , Wang Shugang , Gu Weiyue , Sun Dan , Gao Feng TITLE=Expanding the Phenotypic and Genotypic Spectrum of ARFGEF1-Related Neurodevelopmental Disorder JOURNAL=Frontiers in Molecular Neuroscience VOLUME=15 YEAR=2022 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.862096 DOI=10.3389/fnmol.2022.862096 ISSN=1662-5099 ABSTRACT=

Mono-allelic loss-of-function variants in ARFGEF1 have recently caused a developmental delay, intellectual disability, and epilepsy, with varying clinical expressivity. However, given the clinical heterogeneity and low-penetrance mutations of ARFGEF1-related neurodevelopmental disorder, the robustness of the gene-disease association requires additional evidence. In this study, five novel heterozygous ARFGEF1 variants were identified in five unrelated pediatric patients with neurodevelopmental disorders, including one missense change (c.3539T>G), two canonical splice site variants (c.917-1G>T, c.2850+2T>A), and two frameshift (c.2923_c.2924delCT, c.4951delG) mutations resulting in truncation of ARFGEF1. The pathogenic/likely pathogenic variants presented here will be highly beneficial to patients undergoing genetic testing in the future by providing an expanded reference list of disease-causing variants.