Late-onset bilateral lens dislocation and glaucoma associated with a novel mutation in FBN1

PURPOSE: To describe the clinical and genetic findings in one Chinese family with late-onset bilateral lens dislocation and secondary glaucoma. METHODS: One family including three affected members and 16 unaffected family members was examined clinically. After informed consent was obtained, genomic DNA was extracted from venous blood of all participants. Linkage analysis was performed with two microsatellite markers around the fibrillin-1 (FBN1) gene (D15S992 and D15S126). Mutation screening was performed using direct DNA sequence analysis and single strand conformation polymorphism (SSCP). RESULTS: Clinical examination and pedigree analysis revealed that four members in three generations were affected by late-onset lens dislocation and secondary glaucoma but had no signs of cardiovascular abnormality or abnormal skeletal features. By genotyping, the family showed the linkage to FBN1 on 15q21.1. After mutation screening analysis on 65 exons of FBN1, a novel heterozygous missense mutation, c.2860C>T (R954C), was detected. This mutation cosegregated with the disease phenotype in the family and was not found in 100 normal controls. CONCLUSIONS: Late-onset isolated ectopia lentis with secondary glaucoma is consistent with a novel mutation in FBN1. Our finding expands the spectrum of FBN1 mutations and is useful for further genetic consultation and genetic diagnosis.