摘要
目的对马方综合征家系的临床特征进行分析,探索该家系的致病基因及突变位点。方法收集2017年在我院就诊的1个马方综合征家系,抽取家系中每个与先证者有血缘关系的成员外周静脉血,提取全基因组DNA,对先证者进行靶向捕获高通量测序获得突变位点,对筛选出的可疑突变扩展至家系全体成员进行Sanger测序验证。结果除升主动脉扩张表现外,测序结果发现家系中马方综合征患者编码原纤维蛋白1(fibrillin-1)的FBN1(NM-00138.4)第38号外显子有杂合截短突变c.4621C>T(p.R1541*)。另外发现可能致病的TCF4(NM_001243230.1)基因第1外显子杂合移码突变c.62dupA(p.N21Kfs*2)和IARS(NM_013417.3)第4外显子杂合截短突变c.361C>T(p.R121*)。结论与数据库中数据对比,FBN1基因可能为该家系的致病基因,第38号外显子(序列NM-00138.4)c.4621C>T(p.R1541*)突变为中国人群首次报道,本研究扩展了FBN1基因导致中国人群患马方综合征的突变谱。
Objective We aim to analyze the clinical characteristics of a family with Marfan's syndrome,and to explore the pathogenic genes and mutation sites of this family.Method We collected a family with Marfan’s syndrome in our hospital in 2017.After signing of the informed consent,each in the line of the propositus related was extracted from peripheral venous blood.The members of the extraction of genome DNA,to target capture propositus,were high-throughput sequenced for mutations to screen out the suspicious mutation verifies the Sanger sequencing extended to family members.Results In addition to the dilatation of ascending aorta,heterozygous truncation mutation C.4621C>T(P.r1541*)was found in exon 38 of FBN1(NM-00138.4)in the family of Marfan’s syndrome patients.In addition,heterozygous code transfer mutation C.62dupA(P.n21kFS*2)in exon 1 of TCF4 gene and heterozygous truncation mutation C.361C>T(P.R121*)in exon 4 of IARS gene were found.Conclusion FBN1 gene may be the pathogenic gene in this family.The mutation of exon 38(sequence NM-00138.4)C.4621C>T(P.r1541*)was reported for the first time in Chinese population.This study extended the mutation spectrum of Marfan syndrome in Chinese population caused by FBN1 gene.
作者
赵向东
金经
管翔
李庆国
ZHAO Xiang-dong;JIN Jing;GUAN Xiang;LI Qing-guo(Department of Cardiovascular Surgery,The Second Affiliated Hospital of Nanjing Medical University,Nanjing 210000,China)
出处
《中国心血管病研究》
CAS
2022年第8期697-700,共4页
Chinese Journal of Cardiovascular Research
基金
国家自然科学基金面上项目(82170503)
南京医科大学基金面上项目(2017NJMUZD036)。
