Clinical variability of XXXX reflecting molecular heterogeneity: @entity462 substitutions in the alpha 1(I) collagen chain producing lethal and mild forms.

@entity1 @entity462 @entity6927 @entity3208 @entity2228 @entity4022 @entity12553 @entity69642 @entity1520 @entity6926 @entity1473
We have examined the collagenous proteins extracted from skin and produced by skin fibroblast cultures from the members of a family with mild @entity6926 ( @entity69642 ). The two affected @entity1 , mother and son, produce two populations of alpha 1(I) chains of type I collagen, one chain being normal, the other containing a @entity462 within the triple-helical domain. Both forms can be incorporated into triple-helical molecules with an alpha 2(I) chain. When two mutant alpha (I) chains are incorporated into the same molecule, a @entity1520 bonded dimer is produced. We have characterized these chains by @entity3208 -gel electrophoresis and CNBr-peptide mapping and by measuring a number of biosynthetic and physical variables. The @entity462 was localized to the @entity1473 -terminal peptide alpha (I) CB6. Molecules containing the mutant chains are stable, have a normal denaturation temperature, are secreted normally, and have normal levels of post-translational modification of @entity12553 residues and intracellular degradation. We have compared and contrasted these observations with those made in a @entity1 with lethal @entity6926 in which there was a @entity462 substitution in @entity6927 (Steinmann, B., Rao, V. H., Vogel, A., Bruckner, P., Gitzelmann, R., and Byers, P. H. (1984) J. Biol. Chem 259, 11129-11138) and have concluded that the mutation in the present family occurs in the X or Y position of a @entity4022 -X-Y repeating unit of collagen and not in the @entity2228 position shown for the previous @entity1 (Cohn, D. H., Byers, P. H., Steinmann, B, and Gelinas, R. E. (1986) Proc. Natl. Acad. Sci. U. S. A., in press.
