title: Detection of 53 FBN1 mutations (41 novel and 12 recurrent) and genotype-phenotype correlations in 113 unrelated probands referred with Marfan syndrome, or a related fibrillinopathy.
abstract: Mutations in the gene encoding fibrillin 1 (FBN1) cause Marfan syndrome (MFS), and related connective tissue disorders. The disease spectrum is wide and while many genotype-phenotype correlations have been reported, few have been consistent. In this study FBN1 was analyzed in 113 patients with MFS or Marfan-like features. Fifty-three mutations were identified in 52 individuals, 41 of which were novel. The mutations comprised 26 missense, 11 splice site, 7 frameshift, 6 nonsense, 1 in-frame deletion, and 2 whole exon deletions. In common with previous studies, genotype-phenotype analysis showed that a FBN1 mutation was more likely to be identified in patients fulfilling Ghent criteria (P = 0.005) and in those who had ectopia lentis (EL) (P < 0.0001). Other previously reported genotype-phenotype correlations were also considered and a new inverse association between a mutation in exons 59-65, and EL emerged (P = 0.002).
authors.affiliation: Princess Anne Hospital Service, Wessex Clinical Genetics, Level G, Southampton, UK. clsturner1@yahoo.co.uk
authors.forename: C L S
authors.initials: CL
authors.lastname: Turner
authors.forename: H
authors.initials: H
authors.lastname: Emery
authors.forename: A L
authors.initials: AL
authors.lastname: Collins
authors.forename: R J
authors.initials: RJ
authors.lastname: Howarth
authors.forename: C M
authors.initials: CM
authors.lastname: Yearwood
authors.forename: E
authors.initials: E
authors.lastname: Cross
authors.forename: P J
authors.initials: PJ
authors.lastname: Duncan
authors.forename: D J
authors.initials: DJ
authors.lastname: Bunyan
authors.forename: J F
authors.initials: JF
authors.lastname: Harvey
authors.forename: N C
authors.initials: NC
authors.lastname: Foulds
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003240:Connective Tissue Diseases; D004252:DNA Mutational Analysis; D004479:Ectopia Lentis; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005838:Genotype; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D055815:Young Adult; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines