What is Osteogenesis imperfecta is a group of diseases characterized by genetic mutations which lead to? and explain in detail?
Collagen is a fibrous protein composed of 3 chains which form the collagen triple helix. Several different types of collagen exist which vary in the types and combinations of the 3 chains forming the collagen helix. Each collagen chain is the product of separate genes. For example, the type of collagen found in skin, aeries, bone, and tendons, Type I Collagen, is composed of 2 a1(I) chains and 1 a2(I) chain. Every third amino acid residue of all of the collagen chains is glycine. This allows the chains to intewine with glycine at the center. Osteogenesis imperfecta is a disease consisting of at least 4 clinically, genetically, and biochemically distinguishable disorders. All are characterized by multiple bone fractures which result in bone deformities. Mutations leading to shoened a1(I) chains cause many of these variants. The sho a1(I) chain associates with normal a1(I) chains and a2(I) chains which prevents normal helix formation. Defective molecules are degraded leading to weakened collagen structures. Other forms of osteogenesis imperfecta are due to mutations in which glycine residues are changed to other amino acids. This leads to destabilization of the collagen helix because of the larger amino acid forced to the center of the helix structure. A decrease in hydroxyproline occurs in scurvy. This occurs because ascorbic acid (vitamin C) is necessary to form the hydroxyproline. With decreased amounts of hydroxyproline in the collagen molecule, the helix is less stable. The result is deficient growth and poor wound healing in the individual with scurvy. The disease Ehlers-Danlos VI is characterized by a decrease in the enzyme lysyl hydroxylase, the enzyme responsible for the formation of hydroxylysine. The decrease in hydroxylysine in collagen results in less stable cross-linking of the collagen molecules. Ref: Prockop D.J., Bateman J.F. (2012). Chapter 363. Heritable Disorders of Connective Tissue. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison's Principles of Internal Medicine, 18e.