Human Molecular Genetics, Vol 4, 1799-1809, Copyright © 1995 by Oxford University Press
HC Dietz and RE Pyeritz
The extracellular microfibril, 10-14 nm in diameter, performs a number of
functions, including serving as the scaffolding for deposition of
tropoelastin to form elastic fibers. A variety of proteins compose the
structure of microfibrils, the most prominent of which are the two
fibrillins. Fibrillin-1 is encoded by FBN1 on human chromosome 15q21 and
fibrillin-2 is encoded by FBN2 on 5q23. Each fibrillin monomer contains a
large number of epidermal growth factor-like motifs, most capable of
binding calcium ions, and a few motifs resembling the binding protein for
transforming growth factor beta. In vitro polymerization of fibrillin
monomers produces 'beads on a string' structures that look on electron
microscopy much like microfibrils purified from the extracellular matrices
of a variety of tissues. Mutations in FBN1 produce Marfan syndrome, a
pleiotropic autosomal dominant connective tissue disorder with prominent
manifestations in the skeleton, eye and cardiovascular system. A number of
conditions related to Marfan syndrome are also due to FBN1 mutations.
Contractural arachnodactyly is due to mutations in FBN2. In this paper we
review the published mutations in these genes, preliminary results of
genotype- phenotype correlations, and speculations regarding molecular
pathogenesis.
REVIEWS
Mutations in the human gene for fibrillin-1 (FBN1) in the Marfan syndrome and related disorders
Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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