摘要目的:探讨1例 SPECCIL基因变异所致Teebi眼距过宽综合征1(TBHS1)患儿的临床特点及其致病机制。 方法:选取2021年7月13日于上海交通大学医学院附属儿童医学中心内分泌与遗传代谢科就诊的1例TBHS1患儿为研究对象。回顾分析患儿的临床资料，抽取患儿及其父母的外周静脉血样，采用全外显子组测序(WES)对患儿进行分析，针对候选变异进行Sanger测序家系验证与生物信息学分析。结果:患儿为13岁男性，临床表现为生长发育迟缓。WES检测结果提示患儿 SPECC1L基因存在c.1244A>G杂合变异，Sanger测序验证为新发变异。该变异在HGMD与gnomAD等数据库中均未见收录；经PolyPhen-2、SIFT及Mutation Taster等在线软件预测，该变异可能影响蛋白结构域功能；经PyMOL软件预测，变异型SPECC1L蛋白(p.Gln415Arg)结构稳定性可能降低；参照美国医学遗传学与基因组学学会(ACMG)相关标准与指南，该变异被评级为致病性变异(PM6+PM1+PP4+PM2_Supporting+PP3)。 结论:SPECC1L基因c.1244A>G杂合变异可能是该TBHS1患儿的遗传学病因。该变异的发现拓展了 SPECC1L基因的变异与表型谱，为临床诊断该类患儿提供了更多的参考依据。

abstractsObjective:To explore the clinical characteristics and genetic basis of a child with Teebi hypertelorism syndrome 1 (TBHS1).Methods:A child with TBHS1 who was admitted to the Children′s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine on July 13, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 13-year-old male, had manifested delayed growth and development. WES results revealed that he has harbored a heterozygous c. 1244A>G variant of the SPECC1L gene, which was verified to be de novo in origin. The variant has not been included in the HGMD and gnomAD databases. As predicted by online software including PolyPhen-2, SIFT, and Mutation Taster, the variant may affect the function of protein domain. And PyMOL software has predicted that the structural stability of SPECC1L protein (p.Gln415Arg) might be reduced. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM6+ PM1+ PP4+ PM2_Supporting+ PP3). Conclusion:The heterozygous c. 1244A>G variant of the SPECC1L gene probably underlay the TBHS1 in this child. Above finding has expanded the genotypic and phenotypic spectrum of the SPECC1L gene and provided a basis for the clinical diagnosis of this child.