儿童早老症家系端粒损耗与TERT基因表达  

Relative telomere attrition and gene expression of TERT in progeria syndrome

作　　者：孙向荣 张瑀欣 郭爽 张明智 徐健[1] 舒伟 SUN Xiangrong;ZHANG Yuxin;GUO Shuang;ZHANG Mingzhi;XU Jian;SHU Wei(School of Intelligent Medicine and Biotechnology,Key Laboratory of Medicine Biotechnology and Translational Medicine,Education Repartment of Guangxi Automonous Region,Guilin Medical University,Guilin 541199,China)

机构地区：[1]桂林医学院智能医学与生物技术学院,广西高校医药生物技术与转化医学重点实验室,广西桂林541199

出　　处：《华夏医学》2023年第5期1-6,共6页Acta Medicinae Sinica

基　　金：国家自然科学基金项目(32060157);国家级大学生创新创业训练计划项目(202210601048)。

摘　　要：目的:分析儿童早老症患者及其家系成员外周血白细胞的端粒相对长度和RNA测序(RNA⁃seq)结果,探究儿童早老症端粒损耗及致病分子机制。方法:采集广西壮族自治区贺州地区1个LMNA R527C突变型早老症家系(3名患者和23名正常家系成员)的外周血样本,分离白细胞。提取白细胞DNA,实时荧光定量PCR分析家系成员的端粒相对长度,同时对白细胞进行RNA⁃seq,并进行生物信息学分析。结果:该家系患者的端粒相对长度短于家系同龄成员,端粒相对长度与年龄呈负相关,家系中早老症患者外周血白细胞端粒酶逆转录酶(TERT)基因表达下调,c⁃Fos基因表达上调。结论:外周血TERT基因表达下调可能与早老症患者的端粒损耗相关,c⁃Fos基因表达上调可能在早老症致病的分子机制中起重要作用。Objective:To investigate the relative telomere length and RNA sequencing(RNA⁃seq)of peripheral blood leukocytes from a family with progeria,and to explore the molecular mechanism of this disease as well as its telomere attribution.Methods:The peripheral blood samples were collected from a LMNA R527C mutant family with progeria(3 patients and 23 normal family members)in Hezhou,Guangxi Zhuang Autonomous Region.White blood cells were isolated and its DNA were extracted.The relative telomere length of the family members was analyzed using real⁃time fluorescence quantitative PCR.At the same time,the RNA⁃seq on white blood cells from patients were performed,its data were analyzed by bioinformatics.Results:The relative telomere length of the three patients was shorter than that of its peers,and there was a negative correlation between the relative telomere length and the age of the family members.The gene expression of telomerase reverse transcriptase(TERT)was down⁃regulated,while the c⁃Fos gene expression was up⁃regulated.Conclusion:The down⁃regulation of TERT gene expression may be related to telomere attrition in the peripheral blood leukocytes of patients with progeria,but the up⁃regulation of c⁃Fos gene expression might play an important role in the molecular mechanism of porgeria.

关 键 词：儿童早老症 LMNA 端粒 端粒酶逆转录酶 

分 类 号：R339.3[医药卫生—人体生理学]