title: Novel FBN1 mutations are responsible for cardiovascular manifestations of Marfan syndrome.
abstract: 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.
authors: 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.
authors: Jin'e
authors: J
authors: Wang
authors: 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.
authors: Yupeng
authors: Y
authors: Yan
authors: 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.
authors: Jinxing
authors: J
authors: Chen
authors: 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.
authors: Ling
authors: L
authors: Gong
authors: 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.
authors: Yu
authors: Y
authors: Zhang
authors: 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.
authors: Mengmeng
authors: M
authors: Yuan
authors: 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.
authors: Bing
authors: B
authors: Cui
authors: 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. yibowang@hotmail.com.
authors: Yibo
authors: Y
authors: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000784:Aortic Dissection / Q000235:genetics*; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002681:China; D005091:Exons; D005260:Female; D000071838:Fibrillin-1 / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D055815:Young Adult; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: FBN1; Genotype; Marfan syndrome; Phenotype