Wang Jin'e, Yan Yupeng, Chen Jinxing, Gong Ling, Zhang Yu, Yuan Mengmeng, Cui Bing, Wang Yibo
College of Medical Science, China Three Gorges University, Yichang, Hubei, China.
State Key Laboratory of Cardiovascular Disease, Sino-German Laboratory for Molecular Medicine, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Rd, Beijing, 100037, China.
Mol Biol Rep. 2016 Nov;43(11):1227-1232. doi: 10.1007/s11033-016-4067-y. Epub 2016 Aug 24.
The fibrillin-1 (FBN1) gene mutations result in Marfan syndrome (MFS) and have a variety of phenotypic variations. This disease is involved in the skeletal, ocular and cardiovascular system. Here we analyzed genotype-phenotype correlation in two Chinese families with MFS. Two patients with thoracic aortic aneurysms and dissections were diagnosed as MFS according to the revised Ghent criteria. Peripheral blood samples were collected and genomic DNAs were isolated from available cases, namely, patient-1 and his daughter and son, and patient-2 and his parents. According to the next-generation sequencing results, the mutations in FBN1 were confirmed by direct sequencing. A heterozygous frameshift mutation in exon 12 of FBN1 was found in the proband-1 and his daughter. They showed cardiovascular phenotype thoracic aortic aneurysms and dissections, a life-threatening vascular disease, and atrial septal defect respectively. One de novo missense mutation in exon 50 of FBN1 was identified only in the patient-2, showing aortic root aneurysm and aortic root dilatation. Intriguingly, two novel mutations mainly caused the cardiovascular complications in affected family members. No meaningful mutations were found in these two patients by screening all exons of 428 genes related with cardiovascular disease. The high incidence of cardiovascular manifestations might be associated with the two novel mutations in exon 12 and 50 of FBN1.
原纤蛋白-1（FBN1）基因突变导致马凡综合征（MFS），并具有多种表型变异。这种疾病累及骨骼、眼睛和心血管系统。在此，我们分析了两个中国马凡综合征家系的基因型-表型相关性。根据修订的根特标准，两名患有胸主动脉瘤和夹层的患者被诊断为马凡综合征。采集外周血样本，从可用病例中分离基因组DNA，即患者1及其女儿和儿子，以及患者2及其父母。根据下一代测序结果，通过直接测序确认了FBN1中的突变。在先证者1及其女儿中发现FBN1第12外显子的杂合移码突变。他们分别表现出心血管表型胸主动脉瘤和夹层（一种危及生命的血管疾病）以及房间隔缺损。仅在患者2中鉴定出FBN1第50外显子的一个新发错义突变，表现为主动脉根部瘤和主动脉根部扩张。有趣的是，两个新突变主要导致受影响家庭成员出现心血管并发症。通过筛查与心血管疾病相关的428个基因的所有外显子，在这两名患者中未发现有意义的突变。心血管表现的高发生率可能与FBN1第12和50外显子的两个新突变有关。
