Detection of 53 FBN1 Mutations (41 Novel and 12 Recurrent) and Genotype-Phenotype Correlations in 113 Unrelated Probands Referred With Marfan Syndrome, or a Related Fibrillinopathy

Mutations in the gene encoding fibrillin 1 (FBN1) cause Marfan syndrome (MFS), and related connective tissue disorders. The disease spectrum is wide and while many genotype-phenotype correlations have been reported, few have been consistent. In this study FBN1 was analyzed in 113 patients with MFS or Marfan-like features. Fifty-three mutations were identified in 52 individuals, 41 of which were novel. The mutations comprised 26 missense, I I splice site, 7 frameshift, 6 nonsense, I in-frame deletion, and 2 whole exon deletions. In common with previous studies, genotype-phenotype analysis showed that a FBN1 mutation was more likely to be identified in patients fulfilling Ghent criteria (P = 0.005) and in those who had ectopia lentis (EL) (P < 0.0001). Other previously reported genotype-phenotype correlations were also considered and a new inverse association between a Mutation in exons 59-65, and EL emerged (P = 0.002). (c) 2009 Wiley-Liss, Inc.