Large kindred with Ehlers-Danlos syndrome type IV due to a point mutation (G571S) in the COL3A1 gene of type III procollagen: Low risk of pregnancy complications and unexpected longevity in some affected relatives

Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant connective ti ssue disorder. Early morbidity and mortality results from rupture of vessel s and internal organs. A large kindred with EDS type IV was studied clinica lly and the biochemical defects and underlying mutation in the COL3A1 gene that encodes the chains of type III procollagen were identified. A G-->A tr ansition results in a single amino acid substitution, G571S, in the triple helical domain of the products of one COL3A1 allele. Although the clinical findings seen on examination are characteristic of EDS type IV, longevity i s longer than that seen in many families and there is less pregnancy-associ ated morbidity or mortality than in some families. This suggests that some clinical aspects of EDS type IV may be related to the nature of the mutatio n and its effect on the behavior of the protein, Am. J. Med. Genet. 82:305- 311, 1999, (C) 1999 Wiley-Liss, Inc.