Purpose: To identify the genetic defect in an autosomal dominant ectopia lentis (EL) family having 27 affected members in four generations.
Methods: Detailed family history and clinical data were recorded for 48 family members including 24 persons with isolated ectopia lentis. Candidate gene regions at 5q and 15q known to be linked with ectopia lentis were analyzed using fluorescent labeled microsatellite markers. Mutation screening in the candidate gene, fibrillin-1 (FBN1), at 15q was performed by bidirectional sequencing of the amplified products.
Results: A maximum LOD score of 5.74 at theta=0.0 was obtained with marker D15S1024 in close proximity to FBN1 at 15q21. Mutation screening in FBN1 identified a C>T transition at nucleotide position c.718. This nucleotide change resulted in the substitution of highly conserved arginine by cysteine at codon 240 (R240C). This nucleotide substitution was not seen in any unaffected member of the family.
Conclusions: We report a recurrent R240C mutation in FBN1 in an autosomal dominant ectopia lentis family. This mutation has previously been reported in a family with isolated ectopia lentis, in another family with ectopia lentis and involvement of the skeleton and integument, and in one person with classic Marfan syndrome. This is the largest family with isolated ectopia lentis reported to date. The results of the present study provide convincing evidence for a correlation of R240C and isolated ectopia lentis. In addition, this is the first report of molecular characterization in an ectopia lentis family of Indian origin.