Purpose: To identify the genetic defect in an autosomal dominant isolated ectopia lentis (EL) family.
Methods: Detailed family history and clinical data were collected from the family including sixteen patients with isolated EL. Blood samples of nine patients, one normal person and two unknown children's were collected. Genomic DNA was extracted from leukocytes of peripheral blood. Genotyping was performed by microsatellite markers and logarithm-of-odds (LOD) scores were calculated using the LINKAGE Programs. Mutation screening in the candidate gene, fibrillin-1 (FBN1), was performed by direct sequencing.
Results: Linkage to the FBN1 locus is verified. Mutation screening in FBN1 identified a C>T transition at nucleotide position c.2920. This nucleotide change results in the cysteine substitution for highly conserved arginine at codon 974 (p.R974C). This mutation is identified in all affected individuals but is not found in 50 control healthy people.
Conclusions: A novel mutation of FBN1 results in an arginine to cysteine residue (p.R974C) substitution, which is responsible for the patients with isolated EL in this Chinese family.