title: Identification of a novel FBN1 gene mutation in a large Pakistani family with Marfan syndrome.
abstract: OBJECTIVE
  To describe a novel mutation in the fibrillin-1 (FBN1) gene in a large Pakistani family with autosomal dominant Marfan syndrome (MFS).
  
  
  METHODS
  Blood samples were collected of 11 family members affected with Marfan syndrome, and DNA was isolated by phenol-extraction. The coding exons of FBN1 were analyzed by polymerase chain reaction (PCR) and direct sequencing. One hundred-thirty controls were screened for a mutation in the FBN1 gene that was identified in this family by restriction fragment length polymorphism (RFLP) analysis.
  
  
  RESULTS
  A novel heterozygous missense mutation c.2368T>A; p.Cys790Ser was observed in exon 19. This mutation substitutes a highly conserved cysteine residue by serine in a calcium binding epidermal growth factor-like domain (cbEGF) of FBN1. This mutation was present in all affected members and absent from unaffected individuals of the family in addition to 130 healthy Pakistani controls. Interestingly all affected family members presented with ectopia lentis, myopia and glaucoma, but lacked the cardinal cardiovascular features of MFS.
  
  
  CONCLUSIONS
  This is a first report of a mutation in FBN1 in MFS patients of Pakistani origin. The identification of a FBN1 mutation in this family confirms the diagnosis of MFS patients and expands the worldwide spectrum of FBN1 mutations.
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Shazia
authors.initials: S
authors.lastname: Micheal
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.forename: Farah
authors.initials: F
authors.lastname: Akhtar
authors.forename: Marjan M
authors.initials: MM
authors.lastname: Weiss
authors.forename: Farah
authors.initials: F
authors.lastname: Islam
authors.forename: Mehmood
authors.initials: M
authors.lastname: Ali
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maugeri
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D003241:Consanguinity; D004479:Ectopia Lentis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005799:Genes, Dominant; D005901:Glaucoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010154:Pakistan; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines