title: Identification of a novel FBN1 gene mutation in a Chinese family with Marfan syndrome.
abstract: OBJECTIVE
  To identify the mutation in the fibrillin-1 gene (FBN1) in a Chinese family with Marfan syndrome (MFS).
  
  
  METHODS
  Patients and family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of six individuals in the family and 170 healthy Chinese individuals. All of the 65 coding exons and their flanking intronic boundaries of FBN1 were amplified in the proband by polymerase chain reaction and followed by direct sequencing. The mutation identified in the proband was screened in the other family members and the 170 healthy Chinese individuals by direct sequencing. Protein conservation analysis was performed in six species using an online ClustalW tool. Protein structure was modeled based on the Protein data bank and mutated in DeepView v4.0.1 to predict the functional consequences of the mutation.
  
  
  RESULTS
  A novel heterozygous c.3703T>C change in exon 29 of FBN1 was detected in the proband, which resulted in the substitution of serine by proline at codon 1235 (p.S1235P). This mutation was also present in two family members but absent in the other, unaffected family members and the 170 healthy Chinese individuals. The mutant residue located in the calcium binding epidermal growth factor-like#15 domain is highly conserved among mammalian species and could probably induce conformation change of the domain.
  
  
  CONCLUSIONS
  We indentified a novel p.S1235P mutation in FBN1, which is the causative mutation for MFS in this family. Our result expands the mutation spectrum of FBN1 and contributes to the study of the molecular pathogenesis of Marfan syndrome.
authors: Department of Ophthalmology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Bo
authors: B
authors: Meng
authors: Hongyi
authors: H
authors: Li
authors: Tao
authors: T
authors: Yang
authors: Shangzhi
authors: S
authors: Huang
authors: Xian
authors: X
authors: Sun
authors: Huiping
authors: H
authors: Yuan
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004479:Ectopia Lentis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006579:Heterozygote; D006801:Humans; D007908:Lens, Crystalline / Q000473:pathology*; D008382:Marfan Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines