Abstract |
Mutations in the FBN1 gene cause Marfan syndrome (MFS) and a wide range of overlapping phenotypes. The severe end of the 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 FBN1 mutation (20%). When comparing patients with mutations leading to a premature termination codon (PTC) 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 PTC 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 heterogeneity could be described for recurrent mutations, ranging from neonatal to classical MFS phenotype. In conclusion, even if the exons 24-32 location appears as a major cause of the severity of the phenotype in patients with a mutation in this region, other factors such as the type of mutation or modifier genes might also be relevant.
|
Authors | L Faivre, G Collod-Beroud, B Callewaert, A Child, C Binquet, E Gautier, B L Loeys, E Arbustini, K Mayer, M Arslan-Kirchner, C Stheneur, A Kiotsekoglou, P Comeglio, N Marziliano, J E Wolf, O Bouchot, P Khau-Van-Kien, C Beroud, M Claustres, C Bonithon-Kopp, P N Robinson, L Adès, J De Backer, P Coucke, U Francke, A De Paepe, G Jondeau, C Boileau |
Journal | European journal of human genetics : EJHG
(Eur J Hum Genet)
Vol. 17
Issue 4
Pg. 491-501
(Apr 2009)
ISSN: 1476-5438 [Electronic] England |
PMID | 19002209
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Codon, Nonsense
- FBN1 protein, human
- Fibrillin-1
- Fibrillins
- Microfilament Proteins
|
Topics |
- Codon, Nonsense
- DNA Mutational Analysis
- Ectopia Lentis
(genetics)
- Exons
(genetics)
- Fibrillin-1
- Fibrillins
- Humans
- Marfan Syndrome
(genetics)
- Microfilament Proteins
(genetics, metabolism)
- Mutation
- Phenotype
|