title: FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders.
abstract: FBN1 encodes the gene for fibrillin-1, a structural macromolecule that polymerizes into microfibrils. Fibrillin microfibrils are morphologically distinctive fibrils, present in all connective tissues and assembled into tissue-specific architectural frameworks. FBN1 is the causative gene for Marfan syndrome, an inherited disorder of connective tissue whose major features include tall stature and arachnodactyly, ectopia lentis, and thoracic aortic aneurysm and dissection. More than one thousand individual mutations in FBN1 are associated with Marfan syndrome, making genotype-phenotype correlations difficult. Moreover, mutations in specific regions of FBN1 can result in the opposite features of short stature and brachydactyly characteristic of Weill-Marchesani syndrome and other acromelic dysplasias. How can mutations in one molecule result in disparate clinical syndromes? Current concepts of the fibrillinopathies require an appreciation of tissue-specific fibrillin microfibril microenvironments and the collaborative relationship between the structures of fibrillin microfibril networks and biological functions such as regulation of growth factor signaling.
authors.affiliation: Departments of Molecular & Medical Genetics and Biochemistry & Molecular Biology, Oregon Health & Science University and Shriners Hospital for Children, 3101 SW Sam Jackson Park Road, Portland, OR 97239, United States. Electronic address: lys@shcc.org.
authors.forename: Lynn Y
authors.initials: LY
authors.lastname: Sakai
authors.affiliation: Biomedical Engineering, Oregon Health & Science University and Shriners Hospital for Children, 3101 SW Sam Jackson Park Road, Portland, OR 97239, United States.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Keene
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Marjolijn
authors.initials: M
authors.lastname: Renard
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: De Backer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000071838:Fibrillin-1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics*; D009154:Mutation / Q000235:genetics
chemical_list: D000071838:Fibrillin-1
keywords: FBN1; Fibrillin; Fibrillinopathies; Marfan syndrome; Microenvironment; Thoracic aortic aneurysm; Weill–Marchesani syndrome