一例Loeys-Dietz综合征患者的超声心动图 表现以及TGFBR1基因变异分析  

Echocardiographic manifestation and analysis of TGFBR1 gene variant in a Chinese patient with Loeys-Dietz syndrome

作　　者：王月丽[1] 牛宝荣[1] 李嵘娟[1] 谢谨捷[1] 李小燕 Wang Yueli;Niu Baorong;Li Rongjuan;Xie Jinjie;Li Xiaoyan(Department of Echocardiography,Beijing Anzhen Hospital Affiliated to Capital Medical University,Beijing 100029,China;Beijing Institute of Heart,Lung and Blood Vessel Diseases,Key Laboratory of Remodeling-related Cardiovascular Diseases of the Ministry of Education,Beijing Anzhen Hospital Affiliated to Capital Medical University,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院超声心动图一部,北京100029 [2]首都医科大学附属北京安贞医院,北京市心肺血管疾病研究所,心血管重塑相关疾病教育部重点实验室,北京100029

出　　处：《中华医学遗传学杂志》2021年第12期1220-1223,共4页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2016YFC0903000);国家自然科学基金(81400846,81501486)。

摘　　要：目的对1例超声心动图提示为主动脉根部瘤及主动脉瓣关闭不全的患者进行基因检测,明确其可能的致病变异,为临床诊断和遗传咨询提供依据。方法应用二代测序技术对先证者进行全外显子组测序,重点分析主动脉瘤疾病及其他循环系统遗传病相关基因,应用Sanger测序对患者及家系成员的疑似致病位点进行检测。依据根据美国医学遗传学与基因组学学会(American College of Medical Geneticsand Genomics,ACMG)遗传变异分类标准与指南判定变异的致病性。结果二代测序结果显示患者的TGFBR1基因(NM_001130916.3)存在c.830T>C杂合变异,而家系正常成员均未检出该变异。SIFT.PolyPhen2和MutationTaster软件分析预测该变异为有害变异,可能导致编码蛋白结构和功能破坏。依据ACMG指南,该变异为可能致病(PM1+PM2+PM6+PP3+PP4)。结论TGFBR1基因c.830 T>C变异可能是该患者致病的原因,基因测序结果为临床诊断和遗传咨询提供了理论依据。Objective To explore the genetic basis for a patient with aortic root aneurysm and valve insufficiency.Methods The patient was subjected to whole exome sequencing(WES)with a focus on the analysis of genes related to aortic aneurysm and other genetic diseases involving the cardiovascular system.Suspected pathogenic site was validated by Sanger sequencing of the patient and his family members.Results WES has revealed a heterozygous c.830T>C variant(NM_001130916.3)in the patient,which was not detected among healthy members of his family.SIFT,PolyPhen2 and Mutation Taster predicted the variant to be disease causing,resulting in destruction of the structure and function of the TGFBR1 protein.Based on the American College of Medical Genetics and Genomics(ACMG)guidelines»the variant was predicted to be likely pathogenic(PM1+PM2+PM6+PP3+PP4).Conclusion The c.830T〉C variant of the TGFBR1 gene probably underlay the disease in the proband.Above finding has enriched the spectrum of TGFBR1 gene variants in Chinese population.

关 键 词：LDS综合征 TGFBR1基因 超声心动图 基因检测 

分 类 号：R593.2[医药卫生—内科学]