title: Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene.
abstract: OBJECTIVE
  To describe the clinical, ocular, and genetic findings in multiple members of a family with early-onset and bilateral lens dislocation, clinical corneal guttae, and glaucoma.
  
  
  METHODS
  All family members underwent complete physical and ophthalmic examinations. After informed consent was given, DNA was obtained from eleven family members, eight of whom were affected. Three polymorphic markers near the fibrillin 1 (FBN1) locus were genotyped and the results analyzed using the VITESSE program. Amplification of the 65 exons and flanking intronic sequences of FBN1 was performed using polymerase chain reaction (PCR), followed by conformation sensitive gel electrophoresis (CSGE). Then, all fragments with mobility variations were sequenced.
  
  
  RESULTS
  Pedigree analysis revealed a three generation family with eight of eleven individuals affected by early onset lens dislocation, high myopia, typical facies, frontal bossing, flexion contractures, proximal interphalangeal (PIP) joint thickening, clinical corneal guttae, and glaucoma. Genetic linkage analysis using polymorphic markers near FBN1 demonstrated an LOD score of 1.78 (maximum possible LOD score 1.78). Conformation sequence gel electrophoresis analysis suggested a sequence variation in exon 3. Sequencing revealed a C965G substitution, resulting in an S322C coding change. This sequence variant segregated with affection status and was not identified in 154 control chromosomes.
  
  
  CONCLUSIONS
  This syndrome is consistent with a novel mutation in the FBN1 gene. FBN1 mutations have been previously described as causative for Marfan syndrome. The early-onset of complete lens dislocation, progressive corneal guttae, and glaucoma is unusual for Marfan syndrome. This study expands the Marfan phenotype and demonstrates a possible link between guttae, glaucoma, and fibrillin 1 disorders.
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA. Chall001@mc.duke.edu
authors.forename: Pratap
authors.initials: P
authors.lastname: Challa
authors.forename: Michael Arthur
authors.initials: MA
authors.lastname: Hauser
authors.forename: Coralia Catalina
authors.initials: CC
authors.lastname: Luna
authors.forename: Sharon Fridovich
authors.initials: SF
authors.lastname: Freedman
authors.forename: Margaret
authors.initials: M
authors.lastname: Pericak-Vance
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Marie Theresa
authors.initials: MT
authors.lastname: McDonald
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D003316:Corneal Diseases / Q000235:genetics; D003545:Cysteine; D005091:Exons; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D008040:Genetic Linkage; D005901:Glaucoma / Q000235:genetics*; D006801:Humans; D007906:Lens Subluxation / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D012694:Serine; D013577:Syndrome; D054392:Adipokines
chemical_list: D003545:Cysteine; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D012694:Serine; C000605722:FBN1 protein, human; D054392:Adipokines