Abstract：
UPF3B encodes the Regulator of nonsense transcripts 3B protein, a core-member of the nonsense-mediated mRNA decay pathway, protecting the cells from the potentially deleterious actions of transcripts with premature termination codons. Hemizygous variants in the UPF3B gene cause a spectrum of neuropsychiatric issues including intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, and schizophrenia/childhood-onset schizophrenia (COS). The number of patients reported to date is very limited, often lacking an extensive phenotypical and neuroradiological description of this ultra-rare syndrome. Here we report three subjects harboring UPF3B variants, presenting with variable clinical pictures, including cognitive impairment, central hypotonia, and syndromic features. Patients 1 and 2 harbored novel UPF3B variants-the p.(Lys207*) and p.(Asp429Serfs*27) ones, respectively-while the p.(Arg225Lysfs*229) variant, identified in Patient 3, was already reported in the literature. Novel features in our patients are represented by microcephaly, midface hypoplasia, and brain malformations. Then, we reviewed pertinent literature and compared previously reported subjects to our cases, providing possible insights into genotype-phenotype correlations in this emerging condition. Overall, the detailed phenotypic description of three patients carrying UPF3B variants is useful not only to expand the genotypic and phenotypic spectrum of UPF3B-related disorders, but also to ameliorate the clinical management of affected individuals.
摘要：
UPF3B编码无义转录物3B蛋白的调节子，无义介导的mRNA衰变途径的核心成员，保护细胞免受具有过早终止密码子的转录本的潜在有害作用。UPF3B基因的半合子变异导致一系列神经精神问题，包括智力障碍，自闭症谱系障碍，注意缺陷多动障碍,和精神分裂症/儿童精神分裂症（COS）。迄今为止报告的患者数量非常有限，通常缺乏对这种超罕见综合征的广泛表型和神经放射学描述。在这里，我们报告了三个携带UPF3B变体的受试者，呈现可变的临床图片，包括认知障碍，中枢低张力,和综合征特征。患者1和2具有新的UPF3B变体-p。（Lys207*）和p。（Asp429Serfs*27），分别-而p.(Arg225Lysfs*229)变体，在文献中已经报道了患者3中的鉴定。我们患者的新特征以小头畸形为代表，脸中部发育不全,大脑畸形.然后，我们回顾了相关文献，并将以前报道的受试者与我们的病例进行了比较，在这种新出现的情况下，为基因型-表型相关性提供可能的见解。总的来说,对三名携带UPF3B变异的患者进行详细的表型描述不仅有助于扩大UPF3B相关疾病的基因型和表型谱，还可以改善受影响个体的临床管理。
