摘要目的:探讨1例 RNASEH2C基因变异所致Aicardi-Goutières综合征3型(AGS 3)患儿的临床特征与遗传学病因。 方法:选取2021年3月27日于湖南省儿童医院就诊的1例AGS3患儿为研究对象。对患儿及其父母进行家系全外显子组测序，并利用Sanger测序对候选变异进行验证。对变异进行晶体结构模拟分析，并构建质粒进行蛋白表达。通过检索文献，总结AGS 3型的表型与遗传学特点。结果:患儿 RNASEH2C基因存在复合杂合变异c.494G>C(p.Ter165Ser)(父源)与c.434G>T(p.Arg145Leu)(母源)，既往均未见报道。蛋白结构预测分析c.434G>T(p.Arg145Leu)变异可能破坏局部结构的稳定性，体外功能实验表明该变异将导致蛋白表达降低。c.494G>C(p.Ter165Ser)变异破坏了终止密码子，导致蛋白产物延长。 结论:本研究发现了两个 RNASEH2C基因的新变异，进一步丰富了AGS 3型的表型与变异谱。

abstractsObjective:To explore the clinical characteristics and genetic etiology of a child with Aicardi-Goutières syndrome 3 (AGS3).Methods:Trio whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. To further clarify their pathogenicity, the crystal structure of the variants was simulated and analyzed, and the plasmid of variants was expressed in vitro. A literature search was also carried out to summarize the phenotypic and genetic characteristics of AGS3. Results:The child was found to harbor novel compound heterozygous variants of the RNASEH2C gene, namely c. 434G>T (p.Arg145Leu) and c. 494G>C (p.Ter165Ser), which were inherited from his mother and father, respectively. Analysis of protein crystal structure suggested that the c. 434G>T (p.Arg145Leu) variant may affect the stability of local structure, and in vitro experiments showed that this variant can lead to protein degradation. The c. 494G>C (p.Ter165Ser) variant has destroyed the stop codon, resulting in prolonged variant. Conclusion:The novel compound heterozygous variants of the RNASEH2C gene probably underlay the AGS3 in this child, which has enriched the phenotypic and mutational spectrum of this disorder.