A recurrent FBN1 mutation in an autosomal dominant ectopialentis family of Indian origin

[摘要] Purpose: To identify the genetic defect in an autosomal dominantectopia lentis (EL) family having 27 affected members in fourgenerations.Methods: Detailed family history and clinical data were recorded for48 family members including 24 persons with isolated ectopia lentis.Candidate gene regions at 5q and 15q known to be linked with ectopialentis were analyzed using fluorescent labeled microsatellite markers.Mutation screening in the candidate gene, fibrillin-1 (FBN1), at 15qwas performed by bidirectional sequencing of the amplified products.Results: A maximum LOD score of 5.74 at θ=0.0 was obtained withmarker D15S1024 in close proximity to FBN1 at 15q21. Mutationscreening in FBN1 identified a C>T transition at nucleotideposition c.718. This nucleotide change resulted in the substitution ofhighly conserved arginine by cysteine at codon 240 (R240C). Thisnucleotide substitution was not seen in any unaffected member of thefamily.Conclusions: We report a recurrent R240C mutation in FBN1 in anautosomal dominant ectopia lentis family. This mutation has previouslybeen reported in a family with isolated ectopia lentis, in anotherfamily with ectopia lentis and involvement of the skeleton andintegument, and in one person with classic Marfan syndrome. This is thelargest family with isolated ectopia lentis reported to date. Theresults of the present study provide convincing evidence for acorrelation of R240C and isolated ectopia lentis. In addition, this isthe first report of molecular characterization in an ectopia lentisfamily of Indian origin.

[学科分类] 生物化学/生物物理