显性遗传智力发育障碍47型(OMIM #617635)与STAG1基因(OMIM*604358)的杂合变异相关，主要临床表现为智力低下、语言发育迟缓、面容异常、癫痫等。本研究报道了1例被诊断为“精神运动发育迟缓”的3岁患儿。利用全外显子组测序技术结合Sanger测序进行基因检测分析发现，该患儿携带STAG1基因c.500dup (p.Gly168TrpfsTer13)为新发变异(其父母均未携带该变异)。根据美国医学遗传学与基因组学学会的遗传变异分类标准与指南，该变异被判定为致病变异(PVS1+PM2_Supporting+PS2_Supporting)。同时，本研究进一步构建突变型质粒表达载体，转染HEK293T细胞，初步发现该变异会导致突变型mRNA表达显著降低，正常STAG1蛋白无法产生。上述研究结果表明，STAG1基因变异导致的临床表型多样，STAG1基因变异的致病机制可能与基因单倍剂量不足相关。

Autosomal dominant intellectual developmental disorder (type 47) (OMIM #617635) is associated with heterozygous variants in the STAG1 gene (OMIM*604358). The main clinical manifestations include intellectual disability, delayed language development, abnormal facial features, epilepsy, etc. In this study, we performed the whole-exome sequencing (WES) on a 3-year-old child diagnosed with psychomotor developmental delay, and verified candidate gene variants by Sanger sequencing. We constructed a mutant plasmid expression vector and subsequently transfected it into HEK293T cells to preliminarily investigate the pathogenic mechanism of the identified variant. Additionally, we conducted a comprehensive review of previously published literature to systematically summarize the associated clinical phenotypes. WES revealed that the patient harbored the c.500dup (p.Gly168TrpfsTer13) of the STAG1 gene, and it was a de novo variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as a pathogenic variant (PVS1+PM2_Supporting+PS2_Supporting). In vitro cellular function studies have demonstrated that this variant resulted in a substantial decrease in the expression of mutant mRNA, thereby impairing the production of functional STAG1 protein. Clinical phenotypes associated with STAG1 gene variants display considerable variability. This study suggests that the pathogenic mechanism of STAG1 gene variants may be linked to haploinsufficiency of the gene.