BackgroundThe majority of Marfan syndrome (MFS) cases is caused by mutations in the fibrillin-1 gene (FBN1), mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature.ResultsWe 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.DiscussionThis 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.

Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes, generally equal in size or smaller than a chromosome 20 of the same metaphase spread. Most of them are unexpectedly detected in routine karyotype analyses, and it is usually not easy to correlate them with a specific clinical picture. A small group of sSMCs is derived from more than one chromosome, called complex sSMCs. Here, we report on a patient with a de novo complex sSMC, derived from chromosomes 8 and 14. Banding karyotype analysis, multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism (SNP)-based array, and fluorescence in situ hybridization (FISH) were performed to investigate its origin. Array and FISH analyses revealed a der(14)t(8;14)(p23.2;q22.1)dn. The propositus presents some clinical features commonly found in patients with partial duplication or triplication of 8p and 14q. This is the first report describing a patient with a congenital der(14)t(8;14)(p23.2;q22.1)dn sSMC.

A small supernumerary marker chromosome (sSMC) derived from chromosome 22 is a relatively common cytogenetic finding. This sSMC typically results in tetrasomy for a chromosomal region that spans the chromosome 22p arm and the proximal 2 Mb of 22q11.21. Using classical cytogenetics, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and array techniques, 7 patients with sSMCs derived from chromosome 22 were studied: 4 non-related and 3 from the same family (mother, daughter, and son). The sSMCs in all patients were dicentric and bisatellited chromosomes with breakpoints in the chromosome 22 low-copy repeat A region, resulting in cat eye syndrome (CES) due to chromosome 22 partial tetrasomy 22pter→q11.2 including the cat eye chromosome region. Although all subjects presented the same chromosomal abnormality, they showed a wide range of phenotypic differences, even in the 3 patients from the same family. There are no previous reports of CES occurring within 3 patients in the same family. Thus, the clinical and follow-up data presented here contribute to a better delineation of the phenotypes and outcomes of CES patients and will be useful for genetic counseling.