title: Two novel mutations of fibrillin-1 gene correlate with different phenotypes of Marfan syndrome in Chinese families.
abstract: OBJECTIVE
  To identify the causative mutations in two Chinese families with autosomal dominant Marfan syndrome and to describe the associated phenotypes.
  
  
  METHODS
  Complete physical, ophthalmic, and cardiovascular examinations were given to the patients and unaffected individuals in the two families. Exclusive linkage mapping was performed for transforming growth factor beta receptor II (TGFBR2) and fibrillin-1 (FBN1) loci in both families. The entire coding region and flanking splice sites of the FBN1 gene were screened for mutations in the two families with Sanger sequencing. The potential mutations of FBN1 were tested in 100 normal controls.
  
  
  RESULTS
  Lens dislocation was observed in two out of ten patients in the MF1 family and all patients in the MF2 family. However, the MF1 family displayed more severe cardiovascular and skeletal system involvement compared with the MF2 family. The transforming growth factor beta receptor II locus was excluded in both families by linkage analysis. A maximum multipoint lod score score of 2.83 was obtained for marker D15S992 (located in the FBN1 gene) in the MF1 family and 1.51 for the same marker in the MF2 family. Two novel mutations of FBN1, p.C271* and p.C637Y, were identified in the MF1 and MF2 families, respectively.
  
  
  CONCLUSIONS
  Genotype-phenotype correlations in this study indicate that nonsense mutations of FBN1 may correlate with relatively severe systemic phenotypes when compared with cysteine substitutions, the most common type of FBN1 mutations. Genetic diagnosis for patients with Marfan syndrome would help with genetic counseling, clinical intervention, and prognosis.
authors.affiliation: Department of Cardiology and Surgery, Tianjin Chest and Heart Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Pan
authors.forename: Kanxing
authors.initials: K
authors.lastname: Zhao
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002681:China; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014463:Ultrasonography; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines