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Identification of novel FBN1 and TGFBR2 mutations in 65 probands with Marfan syndrome or Marfan-like phenotypes

Authors

  • Brian Hon-Yin Chung,

    1. Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Stephen Tak-Sum Lam,

    1. Clinical Genetic Service (CGS), Department of Health, Hong Kong Special Administrative Region, China
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  • Tony Ming-For Tong,

    1. Clinical Genetic Service (CGS), Department of Health, Hong Kong Special Administrative Region, China
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  • Susanna Yuk-Han Li,

    1. Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Kin-Shing Lun,

    1. Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Daniel Hon-Chuen Chan,

    1. Clinical Genetic Service (CGS), Department of Health, Hong Kong Special Administrative Region, China
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  • Susanna Fung-Shan Fok,

    1. Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
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  • June Siu-Fong Or,

    1. Clinical Genetic Service (CGS), Department of Health, Hong Kong Special Administrative Region, China
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  • David Keith Smith,

    1. Department of Biochemistry, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Wanling Yang,

    1. Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Yu-Lung Lau

    Corresponding author
    1. Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
    • Department of Paediatrics & Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
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  • How to cite this article: Chung BH-Y, Lam ST-S, Tong TM-F, Li SY-H, Lun K-S, Chan DH-C, Fok SF-S, Or JS-F, Smith DK, Yang W, Lau Y-L. 2009. Identification of novel FBN1 and TGFBR2 mutations in 65 probands with Marfan syndrome or Marfan-like phenotypes. Am J Med Genet Part A 149A:1452–1459.

Abstract

Marfan syndrome is an autosomal dominant connective tissue disorder, and mutations in the FBN1 and TGFBR2 genes have been identified in probands with MFS and related phenotypes. Using DHPLC and sequencing, we studied the mutation spectrum in 65 probands with Marfan syndrome and related phenotypes. A total of 24 mutations in FBN1 were identified, of which 19 (nine missense, six frameshift, two nonsense and two affecting splice junctions) were novel. In the remaining 41 probands, six were identified to have novel TGFBR2 mutations (one frameshift and five missense mutations). All novel mutations found in this study were confirmed to be absent in 50 unrelated normal individuals of the same ethnic background. In probands who fulfilled the Ghent criteria (n = 16), mutations in FBN1 were found in 81% of cases. None of those with TGFBR2 mutations fulfilled the Ghent criteria. Novel missense mutations of unknown significance were classified according to the latest ACMG guidelines and their likelihood to be causative was evaluated. © 2009 Wiley-Liss, Inc.

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