摘要目的:探讨1例罕见的 ABCC6基因变异所致婴儿泛发性动脉钙化(GACI)患儿的临床表现与遗传学病因。 方法:选取2022年8月26日就诊于首都医科大学附属北京儿童医院保定医院的1例44 d女性患儿作为研究对象。收集患儿的临床资料，通过核心家系全外显子组测序(Trio-WES)、全基因组拷贝数变异测序(CNV-seq)以及Minigene剪接实验对变异进行致病性分析。结果:患儿主要表现为发热、炎症指标高、抗感染治疗无效，超声显示全身大、中动脉广泛钙化、管壁增厚，考虑为GACI以及相关的动脉炎，经糖皮质激素、生物制剂治疗后发热缓解。Trio-WES发现患儿携带 ABCC6基因复合杂合变异c.4404-1G>A与c.4041＋5G>T，后者既往未见报道。根据美国医学遗传学与基因组学学会(ACMG)相关指南，两个变异被分别判定为可能致病性(PVS1＋PM2_Supporting)与临床意义不明(PM2_Supporting＋PM3＋PP3)。CNV-seq检测未见异常。Minigene剪接实验进一步验证两个变异均可影响剪接。 结论:对于不明原因及常规治疗无效的发热，需要及时完善基因检测，避免GACI的漏诊。

abstractsObjective:To explore the clinical manifestations and genetic basis for a rare case of Generalized arterial calcification of infancy (GACI).Methods:A 44-day-old female infant who was treated at Baoding Hospital of Beijing Children′s Hospital Affiliated to Capital Medical University on August 26, 2022 was selected as the study subject. Clinical data of the child was collected, and Trio-whole exome sequencing (Trio-WES), whole genome copy number variation sequencing (CNV-seq) and minigene splicing assay were carried out to analyze the pathogenicity of the variants.Results:The child had presented with fever and high inflammatory indicators, for which treatment with various antibiotics was ineffective. Ultrasound had revealed extensive arterial calcification and arterial wall thickening. The child was suspected for GACI with arteritis related to the primary disease. Her fever was relieved by treatment with glucocorticoid and biological agents. Trio-WES revealed that she has harbored compound heterozygous variants of the ABCC6 gene, namely c. 4404-1G>A and c. 4041+ 5G>T, for which the latter was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variants were classified as likely pathogenic (PVS1+ PM2_Supporting) and variant of unknown significance (PM2_Supporting+ PM3+ PP3), respectively. The result of CNV-seq was negative. And the minigene splicing assay has further verified that both variants can result in alternative splicing. Conclusion:For pyrexia with unknown causes and refractory to conventional treatment, it is necessary to recommend early genetic testing to avoid missed diagnosis of GACI.