Brittle bones--fragile molecules: disorders of collagen gene structure and expression

Abstract

Mutations in the genes that encode the chains of type I collagen, the major structural protein in most tissues, usually produce brittle bones. The consequences of even apparently minor mutations--single base substitutions--can range from lethal to mild, and the phenotypic consequences reflect the nature and position of the mutation. The manner in which phenotypes are produced depends on the effect of the mutation on the structural integrity of the molecule and on whether or how the abnormal molecules can be incorporated into an extracellular matrix.