Two novel FBN1 mutations associated with ectopia lentis and marfanoid habitus in two Chinese families

摘要

Purpose: To identify the moleculardefects in the fibrillin-1 gene (FBN1) in two Chinese familieswith ectopia lentis (EL) and marfanoid habitus. Methods: Five patients and eightnon-carriers in the two families underwent complete physical,ophthalmic, and cardiovascular examinations. Genomic DNA was extractedfrom leukocytes of venous blood of these individuals in the families aswell as 100 healthy normal controls. Polymerase chain reaction (PCR)amplification and direct sequencing of all 65 coding exons of FBN1were analyzed. The functional consequences of the mutations wereanalyzed with various genomic resources. Results: Two novel mutations of FBN1were identified in our study. One is a splice defect in intron 17 (IVS17–1GT) adjacent to exon 18. The other is c.6182GT in exon 50,which results in the substitution of cysteine by phenylalanine at codon2,061 (p. C2061F). We provided strong evidences that the splicemutation would potentially lead to the skipping of exons after intron17 and that the missense mutation at codon 2,061 (p. C2061F) woulddestroy a disulfide bond. Conclusions: We detected two novelmutations in FBN1. Our results expand the mutation spectrum of FBN1and help in the study of the molecular pathogenesis of Marfan syndromeand Marfan-related disorders.