title: A FBN1 mutation association with different phenotypes of Marfan syndrome in a Chinese family.
abstract: BACKGROUND
  Previous studies demonstrated that patients with different FBN1 mutations often present more considerable phenotypic variation compared to different members of the related family carrying a same mutation. The purpose of our study was to identify pathogenic mutation and provide more information about genotype-phenotypic correlations in a large Chinese family with Marfan syndrome.
  
  
  METHODS
  15 related family members from a Chinese 4-generation pedigree with Marfan syndrome underwent physical, ophthalmologic, radiological and cardiovascular examinations. The propositus has De Bakey III aortic dissection and didn't fulfill the revised Ghent criteria for Marfan syndrome. Nine family members have ectopia lentis and their echocardiogram was normal. Five other family members have no evidence of Marfan syndrome. Genomic DNA was isolated from blood leukocytes. The exome sequencing was employed on the propositus, then the Sanger sequencing was conducted for mutation verification in other 14 participants of this family.
  
  
  RESULTS
  The causative mutation in FBN1 discovered in the propositus was a known heterozygous missense mutation, c.1633T>G (p.R545C), in exon 14 (NM 000138). This same mutation was also identified in all 9 ectopia lentis patients and one unaffected 8-year-old girl. However, the same mutation was not discovered in other 4 unaffected family members.
  
  
  CONCLUSIONS
  Our data enhance the information of genotype-phenotype correlation owing to FBN1 mutations. To our current knowledge, we firstly reported that the same FBN1 mutation, c. 1633C>T (Arg545Cys), was detected simultaneously in three different cardinal phenotypes (ectopia lentis, aortic dissection and unaffected) within one family. The unaffected girl with FBN1 mutation may presumably represent a rare case of nonpenetrance.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Du
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China. Electronic address: xingqinghe@hotmail.com.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: zhangyanzhou2050@sina.com.
authors.forename: Yanzhou
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D004479:Ectopia Lentis / Q000235:genetics; D005260:Female; D000071838:Fibrillin-1 / Q000235:genetics*; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: Ectopia lentis; FBN1; Marfan syndrome; Mutation