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

[摘要] Purpose: To describe the clinical, ocular, and genetic findings inmultiple members of a family with early-onset and bilateral lensdislocation, clinical corneal guttae, and glaucoma.Methods: All family members underwent complete physical andophthalmic examinations. After informed consent was given, DNA wasobtained from eleven family members, eight of whom were affected. Threepolymorphic markers near the fibrillin 1 (FBN1) locus were genotypedand the results analyzed using the VITESSE program. Amplification of the65 exons and flanking intronic sequences of FBN1 was performed usingpolymerase chain reaction (PCR), followed by conformation sensitive gelelectrophoresis (CSGE). Then, all fragments with mobility variationswere sequenced.Results: Pedigree analysis revealed a three generation family witheight of eleven individuals affected by early onset lens dislocation,high myopia, typical facies, frontal bossing, flexion contractures,proximal interphalangeal (PIP) joint thickening, clinical cornealguttae, and glaucoma. Genetic linkage analysis using polymorphic markersnear FBN1 demonstrated an LOD score of 1.78 (maximum possible LODscore 1.78). Conformation sequence gel electrophoresis analysissuggested a sequence variation in exon 3. Sequencing revealed a C965Gsubstitution, resulting in an S322C coding change. This sequence variantsegregated with affection status and was not identified in 154 controlchromosomes.Conclusions: This syndrome is consistent with a novel mutation inthe FBN1 gene. FBN1 mutations have been previously described ascausative for Marfan syndrome. The early-onset of complete lensdislocation, progressive corneal guttae, and glaucoma is unusual forMarfan syndrome. This study expands the Marfan phenotype anddemonstrates a possible link between guttae, glaucoma, and fibrillin 1disorders.

[学科分类] 生物化学/生物物理