Collagen genes and proteins in osteogenesis imperfecta

Type I collagen is a heteropolymer of alpha 1(I) and alpha 2(I) chains, each of which is a separate product of genes localised to chromosomes 17 and 7 respectively. Molecular defects of type I collagen produce a group of inherited disorders of connective tissue primarily affecting bones, which are easily broken and collagen depleted (osteogenesis imperfecta). Sillence classifies these diseases into four groups, two of which are autosomal dominant and relatively mild, the others being either genetic lethals or responsible for very severe progressive disease. Here we describe two specific molecular abnormalities of type I collagen. One, a cysteine substitution in alpha 1(I) collagen, causes a mild Sillence type I disease, the other, a four base deletion in the C terminal extension of alpha 2(I) collagen, causes progressive Sillence type III disease in the homozygously affected patient and mild premature osteoporosis in his clinically symptomless parents. We have briefly reviewed a variety of other similar mutations causing various OI syndromes, which are tabulated, including various helical and non-helical deletions and a variety of structural protein changes. Several restriction fragment length polymorphisms for alpha 2(I) and alpha 1(II) collagens have also been described, and 5' EcoRI and 3' MspI polymorphisms for alpha 2(I) collagen segregate with Sillence type IV OI.