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Fibrillin–2 (FBN2) mutations result in the Marfan–like disorder, congenital contractural arachnodactyly

Nature Genetics volume 11, pages 456–458 (1995)Cite this article

Abstract

Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to Marfan syndrome (MFS) and characterized by arachnodactyly, dolichostenomelia, scoliosis, multiple congenital contractures and abnormalities of the external ears1. In contrast to MFS, CCA does not affect the aorta or the eyes. Two closely related genes, FBN1 located on chromosome 15q15–21.3 and FBN2 located at 5q23–31, encode large fibrillin proteins found in extracellular matrix structures called microfibrils2–4. The MFS is caused by mutations in FBN1, while CCA has been genetically linked to FBN2 (refs 2, 5, 6). We now describe a pair of FBN2 missense mutations in two CCA patients that cause substitution of distinct cysteine residues in separate epidermal growth-factor-like (EGF) repeats. Our study provides final proof of the association between FBN2 mutations and CCA pathology, thus establishing the role of the fibrillin-2 in extracellular matrix physiology and pathology.

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Affiliations

  1. Department of Internal Medicine, University of Texas–Houston Medical School, 6431 Fannin, Houston, Texas, 77030, USA

    Elizabeth A. Putnam & Dianna M. Milewicz

  2. Brookdale Center for Molecular Biology, Mt. Sinai School of Medicine, New York, New York, 10029–6574, USA

    Hui Zhang & Francesco Ramirez

  3. Division of Cardiovascular Research, Texas Heart Institute/St. Luke's Hospital, Houston, Texas, 77030, USA

    Dianna M. Milewicz

Authors
  1. Elizabeth A. Putnam
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  2. Hui Zhang
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  3. Francesco Ramirez
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  4. Dianna M. Milewicz
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Putnam, E., Zhang, H., Ramirez, F. et al. Fibrillin–2 (FBN2) mutations result in the Marfan–like disorder, congenital contractural arachnodactyly. Nat Genet 11, 456–458 (1995). https://doi.org/10.1038/ng1295-456

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