title: FBN1 mutation screening of patients with Marfan syndrome and related disorders: detection of 46 novel FBN1 mutations.
abstract: Fibrillin-1 gene (FBN1) mutations cause Marfan syndrome (MFS), an inherited connective tissue disorder with autosomal dominant transmission. Major clinical manifestations affect cardiovascular and skeletal apparatuses and ocular and central nervous systems. We analyzed FBN1 gene in 99 patients referred to our Center for Marfan Syndrome and Related Disorders (University of Florence, Florence, Italy): 85 were affected by MFS and 14 by other fibrillinopathies type I. We identified mutations in 80 patients. Among the 77 different mutational events, 46 had not been previously reported. They are represented by 49 missense (61%), 1 silent (1%), 13 nonsense (16%), 6 donor splice site mutations (8%), 8 small deletions (10%), and 3 small duplications (4%). The majority of missense mutations were within the calcium-binding epidermal growth factor-like domains. We found preferential associations between The Cys-missense mutations and ectopia lentis and premature termination codon mutations and skeletal manifestations. In contrast to what reported in literature, the cardiovascular system is severely affected also in patients carrying mutations in exons 1-10 and 59-65. In conclusion, we were able to detect FBN1 mutations in 88% of patients with MFS and in 36% of patients with other fibrillinopathies type I, confirming that FBN1 mutations are good predictors of classic MFS.
authors.affiliation: Department of Medical and Surgical Critical Care, Center of the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Disease to Develop Novel Therapies, University of Florence, Florence, Italy. monicattanasioit@yahoo.it
authors.forename: M
authors.initials: M
authors.lastname: Attanasio
authors.forename: I
authors.initials: I
authors.lastname: Lapini
authors.forename: L
authors.initials: L
authors.lastname: Evangelisti
authors.forename: L
authors.initials: L
authors.lastname: Lucarini
authors.forename: B
authors.initials: B
authors.lastname: Giusti
authors.forename: Mc
authors.initials: M
authors.lastname: Porciani
authors.forename: R
authors.initials: R
authors.lastname: Fattori
authors.forename: C
authors.initials: C
authors.lastname: Anichini
authors.forename: R
authors.initials: R
authors.lastname: Abbate
authors.forename: Gf
authors.initials: G
authors.lastname: Gensini
authors.forename: G
authors.initials: G
authors.lastname: Pepe
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines