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

Pratap Challa, Michael Arthur Hauser, Coralia Catalina Luna, Sharon Fridovich Freedman, Margaret A Pericak-Vance, Jun Yang, Maria Theresa McDonald, R. Rand Allingham

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1009-1015
Number of pages7
JournalMolecular Vision
Volume12
StatePublished - Aug 28 2006
Externally publishedYes

Fingerprint

Lens Subluxation
Glaucoma
Mutation
Genes
Marfan Syndrome
Electrophoresis
Exons
Gels
Genetic Linkage
Myopia
Contracture
Pedigree
Informed Consent
Physical Examination
Fibrillin-1
Chromosomes
Joints
Phenotype
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Challa, P., Hauser, M. A., Luna, C. C., Freedman, S. F., Pericak-Vance, M. A., Yang, J., ... Allingham, R. R. (2006). Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene. Molecular Vision, 12, 1009-1015.

Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene. / Challa, Pratap; Hauser, Michael Arthur; Luna, Coralia Catalina; Freedman, Sharon Fridovich; Pericak-Vance, Margaret A; Yang, Jun; McDonald, Maria Theresa; Allingham, R. Rand.

In: Molecular Vision, Vol. 12, 28.08.2006, p. 1009-1015.

Research output: Contribution to journalArticle

Challa, P, Hauser, MA, Luna, CC, Freedman, SF, Pericak-Vance, MA, Yang, J, McDonald, MT & Allingham, RR 2006, 'Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene', Molecular Vision, vol. 12, pp. 1009-1015.
Challa, Pratap ; Hauser, Michael Arthur ; Luna, Coralia Catalina ; Freedman, Sharon Fridovich ; Pericak-Vance, Margaret A ; Yang, Jun ; McDonald, Maria Theresa ; Allingham, R. Rand. / Juvenile bilateral lens dislocation and glaucoma associated with a novel mutation in the fibrillin 1 gene. In: Molecular Vision. 2006 ; Vol. 12. pp. 1009-1015.
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AU - McDonald, Maria Theresa

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