title: Fibrillin-1 (FBN1) gene frameshift mutations in Marfan patients: genotype-phenotype correlation.
abstract: Marfan syndrome (MFS) is a multisystemic disease associated with mutations in the fibrillin-1 gene. Most of the reported mutations are missense substitutions mainly affecting the epidermal growth factor (EGF)-like protein domain structure and the calcium-binding (cb) site. The aim of our study was to investigate the correlation between fibrillin-1 frameshift mutations and the clinical phenotype in patients affected by MFS. In 48 out of 66 Marfan patients a pathogenetic mutation was found. We detected novel mutations causing premature termination codon in exons 19, 37, 40 and 41 of four Italian patients. The first mutation in exon 19 (cbEGF #8 domain) results in a clinical phenotype involving mainly the skeletal and cardiovascular systems. Interestingly, we noticed that, while mutations in exons 37 and 41 (eight cysteine domains #4 and #5) are milder, the mutation in exon 40 (cbEGF #24 domain) is more severe and causes major cardiovascular involvement with thoracic and abdominal aortic aneurysms. It is noteworthy that the degree of the severity in the phenotype of one of our patients and another from the literature carrying a mutation in exon 41 could be explained with alterations in mRNA expression.
authors.affiliation: Dipartimento di Area Critica Medico Chirurgica, sezione Clinica Medica Generale e Cliniche Specialistiche, University of Florence, Viale Morgagni 85, 50134, Florence, Italy. labctrombosi@ao-careggi.toscana.it
authors.forename: G
authors.initials: G
authors.lastname: Pepe
authors.forename: B
authors.initials: B
authors.lastname: Giusti
authors.forename: L
authors.initials: L
authors.lastname: Evangelisti
authors.forename: M C
authors.initials: MC
authors.lastname: Porciani
authors.forename: T
authors.initials: T
authors.lastname: Brunelli
authors.forename: L
authors.initials: L
authors.lastname: Giurlani
authors.forename: M
authors.initials: M
authors.lastname: Attanasio
authors.forename: R
authors.initials: R
authors.lastname: Fattori
authors.forename: C
authors.initials: C
authors.lastname: Bagni
authors.forename: P
authors.initials: P
authors.lastname: Comeglio
authors.forename: R
authors.initials: R
authors.lastname: Abbate
authors.forename: G F
authors.initials: GF
authors.lastname: Gensini
mesh_terms: D000328:Adult; D004247:DNA; D005091:Exons; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D016368:Frameshift Mutation; D005838:Genotype; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics* / Q000503:physiopathology; D008403:Mass Screening; D008840:Microfilament Proteins / Q000235:genetics*; D016254:Mutagenesis, Insertional; D010641:Phenotype; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis; D054392:Adipokines
chemical_list: D004247:DNA; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C000605722:FBN1 protein, human; D054392:Adipokines