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Further evidence for a marfanoid syndrome with neonatal progeroid features and severe generalized lipodystrophy due to frameshift mutations near the 3′ end of the FBN1 gene

Authors

  • Jack Goldblatt,

    Corresponding author
    1. Genetic Services of Western Australia, King Edward Memorial Hospital, University of Western Australia, Perth, Australia
    2. School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
    • Genetic Services of Western Australia, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, WA 6008.
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  • Jill Hyatt,

    1. Genetic Services of Western Australia, King Edward Memorial Hospital, University of Western Australia, Perth, Australia
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  • Caitlin Edwards,

    1. Department of Molecular Genetics, PathWest Laboratory Medicine, Princess Margaret Hospital for Children, Edith Cowan University, Perth, Australia
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  • Ian Walpole

    1. Genetic Services of Western Australia, King Edward Memorial Hospital, University of Western Australia, Perth, Australia
    2. School of Human Genetics, Edith Cowan University, Perth, Australia
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  • How to Cite this Article: Goldblatt J, Hyatt J, Edwards C, Walpole I. 2011. Further evidence for a marfanoid syndrome with neonatal progeroid features and severe generalized lipodystrophy due to frameshift mutations near the 3′ end of the FBN1 gene. Am J Med Genet Part A 155:717–720.

Abstract

We report on a 20-year-old man who presented in infancy with severe generalized lipodystrophy with a progeroid appearance and some Marfanoid features. He subsequently was diagnosed with bilateral lens subluxations at the age of 16 years which prompted analysis of the FBN1 gene. This analysis showed him to have a novel heterozygous, de novo, c.8156_8175del, p.Lys2719ThrfsX12, frameshift mutation in exon 64 of his FBN1 gene. His phenotype is similar to a patient described by Graul-Neumann et al. [2010] who was found to have a de novo, heterozygous, c.8155_8156del deletion in exon 64 of FBN1. Both mutations result in a truncated protein with an extremely charged C-terminus, containing two positive and four negative charges in the last eight amino acids. This most likely has a profound impact on protein–protein interactions, which are very important in the extracellular matrix. The similarities in the phenotypes, and overlapping molecular defects, provides further evidence that the phenotype with features of Marfan syndrome with neonatal progeroid syndrome-like lipodystrophy is a distinct clinical entity due to frameshift mutations in exon 64 of the FBN1 gene. © 2011 Wiley-Liss, Inc.

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