Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Institute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, China.
J Hum Genet. 2023 Dec;68(12):867-874. doi: 10.1038/s10038-023-01196-4. Epub 2023 Sep 22.
The human SET nuclear proto-oncogene (SET) gene is a protein-coding gene that encodes proteins that affects chromatin remodeling and gene transcription. Mutations in the SET gene have been reported to cause intellectual disability (ID) and epilepsy. In this study, we collected and analyzed clinical, genetic, and transcript features of two unrelated Chinese patients with ID. Both patients were characterized by moderate intellectual disability. Whole-exome sequencing identified two novel heterozygous mutations in the SET gene: NM_001122821.1:c.532-3 T > A and NM_001122821.1:c.3 G > C (p.0?). Additionally, RNA sequencing revealed widespread dysregulation of genes involved in NF-kB signaling and neuronal system in these two patients. To our knowledge, this is the first report of SET mutations causing ID in the Chinese population, broadening the genetic and ethnic spectrum of SET-related disorders and highlighting the importance of screening for SET gene variants.
人类 SET 核原癌基因（SET）是一个编码蛋白质的基因，其编码的蛋白质影响染色质重塑和基因转录。已有报道称，SET 基因的突变会导致智力障碍（ID）和癫痫。在这项研究中，我们收集并分析了两名无关联的中国 ID 患者的临床、遗传和转录特征。两名患者均表现为中度智力障碍。全外显子组测序在 SET 基因中发现了两个新的杂合突变：NM_001122821.1：c.532-3T>A 和 NM_001122821.1：c.3G>C（p.0？）。此外，RNA 测序揭示了这两名患者中涉及 NF-kB 信号和神经元系统的基因广泛失调。据我们所知，这是 SET 突变导致中国人 ID 的首例报道，拓宽了 SET 相关疾病的遗传和种族谱，并强调了筛查 SET 基因突变的重要性。
