Progeroid facial features and lipodystrophy associated with a novel splice site mutation in the final intron of the FBN1 gene

Authors

  • Denise Horn,

    Corresponding author
    1. Institut für Medizinische Genetik und Humangenetik, Charité-Universitätsmedizin Berlin, Berlin, Germany
    • Institut für Medizinische Genetik und Humangenetik, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
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  • Peter N. Robinson

    1. Institut für Medizinische Genetik und Humangenetik, Charité-Universitätsmedizin Berlin, Berlin, Germany
    2. Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany
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  • How to Cite this Article: Horn D, Robinson PN. 2011. Progeroid facial features and lipodystrophy associated with a novel splice site mutation in the final intron of the FBN1 gene. Am J Med Genet Part A 155:721–724.

Abstract

The association of progeroid features and lipodystrophy was very recently described in a female adult with additional manifestations of Marfan syndrome. Mutation analysis of the fibrillin I (FBN1) gene revealed a novel heterozygous frameshift mutation at the 3′ end in that patient. Here, we report on a 3.5-year-old girl with progeroid facial signs of neonatal onset, lipodystrophy, large head circumference with corresponding hydrocephaly, and tall stature at the end of infancy. Her facial appearance showed convincing clinical similarities to the above-mentioned case. We identified a novel heterozygous de novo splice site mutation c.8226+1G>T affecting the last intron of FBN1. We suggest a specific clinical entity characterized by progeroid facial features, lipodystrophy, and at least some clinical signs of Marfan syndrome is associated with a subset of mutations located at the 3′ end of FBN1. This phenotype which is different from that of classical Marfan syndrome could be caused by a truncated FBN1 protein which could escape nonsense-mediated RNA decay. © 2011 Wiley-Liss, Inc.

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