An extra cysteine in one of the non-calcium-binding epidermal growth factor-like motifs of the FBN1 polypeptide is connected to a novel variant of Marfan syndrome

Ståhl-Hallengren, C.; Ukkonen, T.; Kainulainen, K.; Kristofersson, U.; Saxne, T.; Tornqvist, K.; Peltonen, L.

Journal of Clinical Investigation 94(2): 709-713


ISSN/ISBN: 0021-9738
PMID: 8040326
Accession: 008145744

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We present here a family with a clinical phenotype resembling Marfan syndrome (MFS), and displaying joint contracture and episodes of knee joint effusions, but lacking the cardiovascular features of the syndrome. The phenotype of this family represents a unique mixture of connective tissue symptoms, some of which are found in classical MFS and some of which are typical of dominant ectopia lentis. Linkage analyses suggested a linkage (LOD score 2.4; theta = 0) between the phenotype of the family and a polymorphic marker in the vicinity of the fibrillin locus on chromosome 15 (FBN1). Furthermore, a novel transition mutation was identified in the FBN1 gene in all the affected members of the family. In contrast to the majority of fibrillin mutations reported so far, this mutation substitutes a cysteine for arginine, producing an extra cysteine in one of the non-calcium-binding EGF-like motifs of the fibrillin polypeptide, most probably disturbing the formation of one of the three disulfide bridges known to be essential for the normal conformation of this motif.