Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15.This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.Marfan syndrome (MFS) is a dominant disorder, mainly caused by mutations in the fibrillin-1 gene (FBN1) located on chromosome 15q21.1. The estimated prevalence of MFS is about 1 in 10000. Approximately 25% of MFS patients are sporadic cases due to new mutations [1,2]. Different tissues and organs can be affected, especially the cardiovascular, skeletal, and ocular systems. Diagnostic criteria are well established and known as the Ghent criteria [3]. However, the inter- and intra-familial variability of the phenotype limits the establishment of genotype-phenotype correlations. To date, more than 1329 FBN1 mutations have been published (http://www.hgmd.cf.ac.uk/ac/gene.php?gene=FBN1 webcite), but only a few are recurring mutations. Missense mutations substituting or creating a cysteine molecule in one of the calcium-binding EGF domains are the most prevalent. The others are frameshift, splice-site, nonsense mutations and in-frame deletions and insertions. Heterozygous mutations in the genes coding for transforming growth factor beta receptors I (TGFBR1) and II (TGFBR2) have also been reported in patients with MFS and MFS-related disorders, indicating genetic heterogeneity [4-6]. Interstitial deletions involving the 15q21.1 band and the FBN1 gene are very rare. To our best knowledge, there are only six reports in the literature describing de