Park Joohyun, Colombo Roberto, Schäferhoff Karin, Janiri Luigi, Grimmel Mona, Sturm Marc, Grasshoff Ute, Dufke Andreas, Haack Tobias B, Kehrer Martin
Institute of Medical Genetics and Applied Genomics, Hertie Institute for Clinical Brain Research, Tübingen, Germany.
Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, Tübingen, Germany.
Mol Syndromol. 2019 Jul;10(4):195-201. doi: 10.1159/000499060. Epub 2019 Apr 3.
Intellectual disability (ID) occurs in approximately 1% of the population. Over the last years, broad sequencing approaches such as whole exome sequencing (WES) substantially contributed to the definition of the molecular defects underlying nonsyndromic ID. Pathogenic variants in , which encodes the human immunodeficiency virus type I enhancer binding protein 2, have recently been reported as a cause of ID, developmental delay, behavioral disorders, and dysmorphic features. HIVEP2 serves as a transcriptional factor regulating NF-ĸB and diverse genes that are essential in neural development. To date, only 8 patients with pathogenic de novo nonsense or frameshift variants and 1 patient with a pathogenic missense variant in have been reported. By WES, we identified 2 novel truncating variants, c.6609_6616delTGAGGGTC (p.Glu2204*) and c.6667C>T (p.Arg2223*), in 2 young adults presenting with developmental delay and mild ID without any dysmorphic features, systemic malformations, or behavioral issues.
智力残疾（ID）在大约1%的人口中出现。在过去几年中，全外显子组测序（WES）等广泛的测序方法极大地推动了对非综合征性智力残疾潜在分子缺陷的定义。编码人类免疫缺陷病毒I型增强子结合蛋白2的基因中的致病变异，最近被报道为智力残疾、发育迟缓、行为障碍和畸形特征的一个病因。HIVEP2作为一种转录因子，调节核因子-κB以及在神经发育中至关重要的多种基因。迄今为止，仅报道了8例携带该基因新生致病性无义或移码变异的患者以及1例携带致病性错义变异的患者。通过全外显子组测序，我们在2名表现出发育迟缓且轻度智力残疾但无任何畸形特征、全身畸形或行为问题的年轻成年人中，鉴定出2种新的截短变异，即c.6609_6616delTGAGGGTC（p.Glu2204*）和c.6667C>T（p.Arg2223*）。
