Clinical and mutation-type analysis from an international series of 198 probands with a pathogenic FBN1 exons 24-32 mutation

Mutations in the gene cause Marfan syndrome (MFS) and a wide range of overlapping phenotypes. The severe end of the FBN1 spectrum is represented by neonatal MFS, the vast majority of probands carrying a mutation within exons 24-32. We previously showed that a mutation in exons 24-32 is predictive of a severe cardiovascular phenotype even in non-neonatal cases, and that mutations leading to premature truncation codons are under-represented in this region. To describe patients carrying a mutation in this so-called neonatal region, we studied the clinical and molecular characteristics of 198 probands with a mutation in exons 24-32 “ ” from a series of 1013 probands with a mutation (20 ). When comparing patients with mutations leading to a premature FBN1 % termination codon within exons 24-32 to patients with an in-frame mutation within the same region, a significantly higher probability of developing ectopia lentis and mitral insufficiency were found in the second group. Patients with a premature termination codon within exons 24-32 rarely displayed a neonatal or severe MFS presentation. We also found a higher probability of neonatal presentations associated with exon 25 mutations, as well as a higher probability of cardiovascular manifestations. A high phenotypic in se rm -0 03 43 92 5, v er si on 1 5 Ju n 20 09 Author manuscript, published in "European Journal of Human Genetics 2009;17(4):491-501" DOI : 10.1038/ejhg.2008.207