Abstract：
ZNF148 gene is a Krüppel-type transcription factor that has transcriptional regulatory function. Heterozygous variant in ZNF148 gene causes an intellectual disability syndrome characterized by global developmental delay, absence, or hypoplasia of corpus callosum, wide intracerebral ventricles, and dysmorphic facial features, while its associations with ASD and ADHD have not been reported. We report a new patient with intellectual disability, autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). The patient had a novel heterozygous truncating variant c.1818dupC (p.Lys607Glnfs*11) in the ZNF148 gene. This variation produces a ZNF148 truncated protein with a deletion of the C-terminal activation domain and may destabilize the protein by affecting the transcriptional activation function. Brain MRI shows normal brain development. Here, we identify a novel ZNF148 heterozygous truncating variant in a patient with distinct phenotypes of ASD and ADHD, which expands the genotype-phenotype spectrum of ZNF148, and indicates ZNF148 is also a potential target gene for ASD.
摘要：
ZNF148基因是一种具有转录调控功能的Krüppel型转录因子。ZNF148基因中的杂合变异导致以整体发育迟缓为特征的智力障碍综合征，缺席,或者call体发育不全，宽脑室，和畸形的面部特征，而其与ASD和ADHD的关联尚未报道。我们报告了一个智力残疾的新病人，自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）。该患者有一个新的杂合截短变体c.1818dupC（p。Lys607Glnfs*11)在ZNF148基因中。这种变化产生具有C末端激活结构域缺失的ZNF148截短的蛋白质,并且可以通过影响转录激活功能使蛋白质不稳定。脑部MRI显示大脑发育正常。这里,我们在具有不同的ASD和ADHD表型的患者中鉴定了一种新的ZNF148杂合截短变体，这扩大了ZNF148的基因型-表型谱，表明ZNF148也是ASD的潜在靶基因。
