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

• Published in: American journal of medical genetics. Part A Vol. 149A; no. 2; pp. 161 - 170
• Main Authors: Turner, C.L.S., Emery, H., Collins, A.L., Howarth, R.J., Yearwood, C.M., Cross, E., Duncan, P.J., Bunyan, D.J., Harvey, J.F., Foulds, N.C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-02-2009; Wiley-Liss
• Subjects: Adolescent; Adult; Biological and medical sciences; Child; Child, Preschool; Connective Tissue Diseases; DNA Mutational Analysis; Ectopia Lentis; FBN1; Female; Fibrillin-1; Fibrillins; Genotype; genotype-phenotype correlation; Humans; Male; Marfan syndrome; Marfan Syndrome - genetics; Medical genetics; Medical sciences; Microfilament Proteins - genetics; Middle Aged; Mutation; Phenotype; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Young Adult; Connective tissue disease; Skin disease; Correlation; Relapse; Typing; Elastic tissue disease; Genotype; Recurrent; Marfan syndrome; Genetic disease; Phenotype; Systemic disease; FBNI; Mutation; Detection; genotype-phenolype correlation
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32593

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). © 2009 Wiley‐Liss, Inc.