The clinical spectrum of complete FBN1 allele deletions
The most common mutations found in FBN1 are missense mutations (56%), mainly substituting or creating a cysteine in a cbEGF domain. Other mutations are frameshift, splice and nonsense mutations. There are only a few reports of patients with marfanoid features and a molecularly proven complete deletion of a FBN1 allele. We describe the clinical features of 10 patients with a complete FBN1 gene deletion. Seven patients fulfilled the Ghent criteria for Marfan syndrome (MFS). The other three patients were examined at a young age and did not (yet) present the full clinical picture of MFS yet. Ectopia lentis was present in at least two patients. Aortic root dilatation was present in 6 of the 10 patients. In three patients, the aortic root diameter was on the 95th percentile and in one patient, the diameter of the aortic root was normal, the cross-section, however, had a cloverleaf appearance. Two patients underwent aortic root surgery at a relatively young age (27 and 34 years). Mitral valve prolapse was present in 4 of the 10 patients, and billowing of the mitral valve in 1. All patients had facial and skeletal features of MFS. Two patients with a large deletion extending beyond the FBN1 gene had an extended phenotype. We conclude that complete loss of one FBN1 allele does not predict a mild phenotype, and these findings support the hypothesis that true haploinsufficiency can lead to the classical phenotype of Marfan syndrome.European Journal of Human Genetics advance online publication, 10 November 2010; doi:10.1038/ejhg.2010.174.
|Note||Article in press - dd November 2010|
|Persistent URL||dx.doi.org/10.1038/ejhg.2010.174, hdl.handle.net/1765/21419|
Hilhorst-Hofstee, Y., Hamel, B.C., Verheij, J.B., Rijlaarsdam, M.E., Mancini, G.M., Cobben, J.M., … Pals, G.. (2010). The clinical spectrum of complete FBN1 allele deletions. European Journal of Human Genetics, 19(3), 247–252. doi:10.1038/ejhg.2010.174