Purpose: To identify the molecular defects in the fibrillin-1 gene (FBN1) in two Chinese families with ectopia lentis (EL) and marfanoid habitus.
Methods: Five patients and eight non-carriers in the two families underwent complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of these individuals in the families as well as 100 healthy normal controls. Polymerase chain reaction (PCR) amplification and direct sequencing of all 65 coding exons of FBN1 were analyzed. The functional consequences of the mutations were analyzed with various genomic resources.
Results: Two novel mutations of FBN1 were identified in our study. One is a splice defect in intron 17 (IVS 17-1G>T) adjacent to exon 18. The other is c.6182G>T in exon 50, which results in the substitution of cysteine by phenylalanine at codon 2,061 (p. C2061F). We provided strong evidences that the splice mutation would potentially lead to the skipping of exons after intron 17 and that the missense mutation at codon 2,061 (p. C2061F) would destroy a disulfide bond.
Conclusions: We detected two novel mutations in FBN1. Our results expand the mutation spectrum of FBN1 and help in the study of the molecular pathogenesis of Marfan syndrome and Marfan-related disorders.