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Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene.

Publication ,  Journal Article
Challa, P; Hauser, MA; Luna, CC; Freedman, SF; Pericak-Vance, M; Yang, J; McDonald, MT; Allingham, RR
Published in: Mol Vis
August 28, 2006

PURPOSE: 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.

Duke Scholars

Published In

Mol Vis

EISSN

1090-0535

Publication Date

August 28, 2006

Volume

12

Start / End Page

1009 / 1015

Location

United States

Related Subject Headings

  • Syndrome
  • Serine
  • Pedigree
  • Ophthalmology & Optometry
  • Mutation, Missense
  • Middle Aged
  • Microfilament Proteins
  • Male
  • Lod Score
  • Lens Subluxation
 

Citation

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Challa, P., Hauser, M. A., Luna, C. C., Freedman, S. F., Pericak-Vance, M., Yang, J., … Allingham, R. R. (2006). Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene. Mol Vis, 12, 1009–1015.
Challa, Pratap, Michael Arthur Hauser, Coralia Catalina Luna, Sharon Fridovich Freedman, Margaret Pericak-Vance, Jun Yang, Marie Theresa McDonald, and R Rand Allingham. “Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene.Mol Vis 12 (August 28, 2006): 1009–15.
Challa P, Hauser MA, Luna CC, Freedman SF, Pericak-Vance M, Yang J, et al. Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene. Mol Vis. 2006 Aug 28;12:1009–15.
Challa, Pratap, et al. “Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene.Mol Vis, vol. 12, Aug. 2006, pp. 1009–15.
Challa P, Hauser MA, Luna CC, Freedman SF, Pericak-Vance M, Yang J, McDonald MT, Allingham RR. Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene. Mol Vis. 2006 Aug 28;12:1009–1015.

Published In

Mol Vis

EISSN

1090-0535

Publication Date

August 28, 2006

Volume

12

Start / End Page

1009 / 1015

Location

United States

Related Subject Headings

  • Syndrome
  • Serine
  • Pedigree
  • Ophthalmology & Optometry
  • Mutation, Missense
  • Middle Aged
  • Microfilament Proteins
  • Male
  • Lod Score
  • Lens Subluxation