U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential pre-mRNA splicing factor in an early step of splicing. Alternative splicing plays an important role in neuronal development, and disorders of RNA processing steps are implicated in neurological disorders. Recently, the large trio whole-exome sequencing study reported U2AF2 as a novel gene significantly associated with developmental disorders: however, the clinical details of patients with U2AF2 variants were not available. Here, we report an individual with a de novo U2AF2 variant (c.445C>T, p.(Arg149Trp)) using trio-based whole-exome sequencing. This residue was positioned in the RNA recognition motif 1 which recognizes a polypyrimidine-tract splice site signal. The patient showed global developmental delay, intellectual disability, epilepsy, short stature, microcephaly, facial dysmorphism, intermittent exotropia, bilateral ptosis, muscle hypotonia and thin corpus callosum, indicating that U2AF2-related disorder could include systemic dysmorphisms, epilepsy and brain malformation along with global developmental delay.

U2 小核 RNA 辅助因子 2 (U2AF2) 是剪接早期步骤中必不可少的前 mRNA 剪接因子。可变剪接在神经元发育中起重要作用，并且 RNA 加工步骤的紊乱与神经系统疾病有关。最近，大型三人组全外显子组测序研究报告称， U2AF2是一种与发育障碍显着相关的新基因：然而，尚无 U2AF2变异患者的临床细节。在这里，我们报告了一个新的U2AF2 个体使用基于 trio 的全外显子组测序的变体 (c.445C>T, p.(Arg149Trp))。该残基位于识别多嘧啶束剪接位点信号的 RNA 识别基序 1 中。患者表现出全面发育迟缓、智力障碍、癫痫、身材矮小、小头畸形、面部畸形、间歇性外斜视、双侧上睑下垂、肌肉张力减退和胼胝体薄，表明U2AF2相关疾病可能包括全身畸形、癫痫和脑畸形以及全球发育迟缓。