%0 Journal Article
%T Characterization of large genomic deletions in the FBN1 gene using multiplex ligation-dependent probe amplification
%A Larissa V Furtado
%A Whitney Wooderchak-Donahue
%A Alan F Rope
%A Angela T Yetman
%A Tracey Lewis
%A Parker Plant
%A Pinar Bayrak-Toydemir
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-119
%X The study included 14 patients from 11 unrelated families with aortic aneurysm. Of those, six patients (including 3 first-degree relatives), fulfilled the revised Ghent criteria for Marfan syndrome, and eight had predominantly aortic aneurysm/dilatation with variable skeletal and craniofacial involvement. MLPA for FBN1, TGF¦ÂR1, and TGF¦ÂR2 was carried out in all patients. A 385 K chromosome 15 specific array was used in two patients with a deletion of the entire FBN1 in order to define its size and boundaries.We identified two novel large deletions in the FBN1 gene in four patients of two unrelated families who met clinical diagnostic criteria for Marfan syndrome. One patient was found to have a FBN1 deletion encompassing exons 1-5. The other three patients had a 542 Kb deletion spanning the whole FBN1 gene and five additional genes (SLC24A5, MYEF2, CTXN2, SLC12A1, DUT) in the chromosome 15.Our findings expand the number of large FBN1 deletions, and emphasize the importance of screening for large genomic deletions in connective tissue disorders featuring aortopathies, especially for those with classic Marfan phenotype.Thoracic aortic aneurysm with dissection is the most common fatal condition involving the aorta [1], and can be syndromic, familial nonsyndromic or sporadic. Mutations in genes related to the structure and function of the aortic wall, such as MYH11 on chromosome 16p12.2-13.3 [2,3], ACTA2 on chromosome 10q23-24 [4], SLC2A10 on chromosome 20q13.1 [5], NOTCH1 on chromosome 9q34-35 [6], TGF¦ÂR1 on chromosome 9q33-34 [7], and TGF¦ÂR2 genes on chromosome 3p24-25 [8] have been linked to non-syndromic familial forms of thoracic aortic aneurysm [reviewed in 9]. Syndromic connective tissue diseases featuring aortic aneurysm and dissection comprise a heterogeneous group of genetic diseases, including Marfan syndrome (MFS; OMIM # 154700), Loeys-Dietz syndrome (LDS; OMIM # 609192), Ehlers Danlos syndrome type IV (EDS IV; OMIM # 130050), and familial thoracic aneurysm
%U http://www.biomedcentral.com/1471-2350/12/119