Iwama Kazuhiro, Kato Mitsuhiro, Uchiyama Yuri, Sakamoto Masamune, Miyamoto Ryosuke, Izumi Yuishin, Ohashi Kei, Hattori Ayako, Yoshida Noboru, Azuma Yoshiteru, Watanabe Akito, Ikeda Chizuru, Shimizu-Motohashi Yuko, Kusabiraki Shohei, Nakagawa Eiji, Sasaki Masayuki, Sugai Kenji, Ohori Sachiko, Tsuchida Naomi, Hamanaka Kohei, Koshimizu Eriko, Fujita Atsushi, Nakashima Mitsuko, Miyatake Satoko, Sengoku Toru, Ogata Kazuhiro, Saitoh Shinji, Saitsu Hirotomo, Ito Shuichi, Mizuguchi Takeshi, Matsumoto Naomichi
Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
J Hum Genet. 2025 Apr;70(4):181-188. doi: 10.1038/s10038-025-01316-2. Epub 2025 Jan 22.
Interferon regulatory factor 2 binding protein-like (IRF2BPL) is a single-exon gene that is ubiquitously expressed in various tissues, including the brain. IRF2BPL encodes a transcription factor with two zinc-finger domains that potentially downregulate WNT signaling in the nervous system. Pathogenic IRF2BPL variants have been reported to cause developmental delay, seizures, myoclonus epilepsies, autistic spectrum disorder, and other neurodevelopmental disorders. Exome sequencing of 10 patients with developmental delay and/or epilepsy from nine families revealed nine pathogenic IRF2BPL variants, of which eight were novel: five missense, one in-frame indel, and three truncating variants. Using reported pathogenic and benign variants, we highlight here several regions of IRF2BPL that deviate in the frequency of pathogenic and benign variants. This study of detailed clinical and genetic information shows that IRF2BPL missense and in-frame indel variants are often associated with seizures and developmental delay.
干扰素调节因子2结合蛋白样蛋白（IRF2BPL）是一个单外显子基因，在包括大脑在内的各种组织中普遍表达。IRF2BPL编码一种具有两个锌指结构域的转录因子，可能会下调神经系统中的WNT信号通路。据报道，致病性IRF2BPL变异可导致发育迟缓、癫痫、肌阵挛性癫痫、自闭症谱系障碍和其他神经发育障碍。对来自九个家庭的10名发育迟缓患者和/或癫痫患者进行外显子组测序，发现了9种致病性IRF2BPL变异，其中8种是新发现的：5种错义变异、1种框内插入缺失变异和3种截短变异。利用已报道的致病性和良性变异，我们在此强调了IRF2BPL中几个致病性和良性变异频率存在差异的区域。这项对详细临床和遗传信息的研究表明，IRF2BPL错义变异和框内插入缺失变异通常与癫痫和发育迟缓有关。
