Studies on collagen metabolism in the Marfan syndrome

Abstract

The pattern of collagen metabolism was studied in nine fibroblast cultures from Marfan patients. The cellular synthesis of collagen and non-collagenous proteins was significantly increased, whereas secretion and degradation remained unchanged. Other steps of post-translational processing such as hydroxylation of prolyl or lysyl residues, affecting triple helix stability, were found to be normal. Furthermore, peptide mapping of isolated a 1(I), a 2(I) and a 1(III) gave no evidence for structural defects. Hence, our study would support the notion that defects other than those affecting collagen type I or III metabolism must represent the molecular basis of the Marfan syndrome.

Marfan syndrome: Absence of type I or III collagen structural defects in 25 patients

“…In addition, we did not observe the slow electrophoretic migrations of collagen chains and peptides, resulting from overmodification of lysine residues, which have been observed with mutations of collagen c~chains in other genetically determined connective tissue diseases . Our finding of apparently normal type I and III collagen chains is in keeping with most of the biochemical studies which have been undertaken using dermis or cultured dermal fibroblasts from patients with the Marfan syndrome (Halbritter et al, 1981;Chemke et al, 1984;Muller et al, 1987). These findings are also in accordance with linkage studies of collagen restriction fragment length polymorphisms with the Marfan phenotype.…”

“…More recently, the proband was shown by eDNA sequencing to be heterozygous for a single change, a G to A, which resulted in the substitution of glutamine for the *Correspondence MS received 31.8.89 Accepted 30.11.89 Harley et al arginine at position 618 in the triple helical domain of the e2(I) chain (Phillips et aI., 1989). In contrast, other reports do not provide evidence of primary structure defects of type I collagen or defects of the other fibrillar type II and III collagens (Tsiporous et al, 1986;Dalgleish et aI., 1987;Muller et al, 1987;Ogilvie et al, 1987).…”