一个GLASS综合征家系致病基因的遗传学分析  

Genetic analysis of pathogenic genes in a family with GLASS syndrome

作　　者：郭敏 郭荣[2] 高景波 曹桂芝 赵晨玥 岳昊 叶婷 薛慧琴 GUO Min;GUO Rong;GAO Jingbo;CAO Guizhi;ZHAO Chenyue;YUE Hao;YE Ting;XUE Huiqin(Department of Pedia-tric Medicine,Shanxi Medical University,Taiyuan 030001,China;Department of Cytogenetic Laboratory,Shanxi Medical University Affiliated Children's Hospital,Shanxi Women and Children Hospital)

机构地区：[1]山西医科大学儿科医学系,太原030001 [2]山西医科大学附属儿童医院,山西省妇幼保健院细胞遗传室

出　　处：《山西医科大学学报》2025年第1期91-97,共7页Journal of Shanxi Medical University

基　　金：复杂遗传病远程协同服务网示范应用项目(SJPT-03-16);山西省回国留学人员科研教研资助项目(2023-180);山西省“四个一批”科技兴医创新计划项目医学遗传学研究委级重点实验室建设项目(2021SYS24);山西省卫生健康委员会资助项目(2023016)。

摘　　要：目的 分析SATB2基因新剪接位点变异导致GLASS综合征一家系的临床和分子遗传学特征,为遗传咨询提供参考。方法 收集和分析GLASS综合征一家系2例患者临床资料;对先证者及其父母进行全外显子组(whole-exome sequencing,WES)和全基因组拷贝数变异(copy number variation,CNV)的二代测序;使用基于人工智能(AI)模型的突变位点剪接预测工具RNA Splicer对变异进行预测评估。通过国内外文献数据库,回顾1989年1月至2023年9月发表的GLASS综合征相关文献。结果 该家系先证者及其母亲有一致的表型:主要临床表现为智力低下,语言发育严重迟缓,社交能力差;面部畸形(长脸、鼻梁突出、球状鼻尖、人中扁平、小嘴、低位耳)和弯曲指。WES测序显示先证者及其母亲携带SATB2 c.1543-1G>A新剪接位点变异,先证者父亲未携带该变异。国内外关于该疾病的报道共47篇,其中9例患者为剪接位点变异。结论 SATB2基因的新剪接位点变异是该家系患者的致病原因,扩大了SATB2基因的变异谱,为该家系的遗传咨询和产前诊断提供依据。Objective To analyze the clinical and molecular genetic characteristics of a family with GLASS syndrome caused by a novel splicing site variation in the SATB2 gene,and provide reference for genetic counseling.Methods Clinical data of two patients with GLASS syndrome in a family were collected and analyzed.Whole-exome sequencing(WES)and genome-wide copy number varia-tion(CNV)were performed on the proband and his parents using next-generation sequencing technology.RNA splicer,an artificial in-telligence(AI)-based mutation splicing prediction tool,was used to predict and assess the mutation.A review of GLASS syndrome-re-lated literature published from January 1989 to September 2023 was conducted through domestic and international literature data-bases.Results The proband and his mother in the family shared consistent phenotypes:mainly intellectual disability,severe delay in language development,and poor social communication skills,facial dysmorphisms(long face,prominent nasal bridge,bulbous nasal tip,flat philtrum,small mouth,low-set ears)and curved fingers.Whole-exome sequencing results showed that the proband and his mother had a novel splice site variant of SATB2 c.1543-1G>A,and the proband's father did not carry the variant.A total of 47 pa-tients were reported in domestic and international literature,and 9 patients had splicing site mutations.Conclusion The new splice site variation of the SATB2 gene is the pathogenic cause of the two patients in this family,which enlarges the variant spectrum of the SATB2 gene and provides a basis for the genetic counseling and the prenatal diagnosis of this family.

关 键 词：SATB2基因 GLASS综合征 SATB2相关综合征 剪接位点变异 Sanger测序 生物信息学分析 全外显子测序分析 

分 类 号：R725[医药卫生—儿科]