Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 177

Osteogenesis imperfecta, or brittle bone disease, is a type 1 collagen disease caused by deficiencies in the synthesis of collagen. It is the most common inherited connective tissue disorder and primarily affects the bone and other tissues rich in collagen (eyes, ears, joints). It is usually an autosomal dominant mutation in the genes that encode the a-1 and a-2 chains of collagen. The genotype-phenotype relationship of the condition depends on the location of the mutation in the protein. Mutations causing a decrease in the amount of normal collagen are associated with mild skeletal abnormalities. More severe forms have polypeptide chains that cannot be arranged in the triple helix. Clinically, four major subtypes exist that vary in severity. Type 1 is compatible with life and has a decreased synthesis of pro-a1(1) chain and abnormal chains. This type is associated with postnatal fractures, skeletal fragility, hearing impairment, and joint laxity. Type 2 is lethal perinataly and the collagen defect is abnormally short pro-a1(1) chain or unstable triple helix. Death in utero or within days of birth, skeletal deformity with excessive fragility, and blue sclera are the major clinical features. Type 3 is progressive and is associated with growth retardation multiple fractures, dentinogenesis imperfecta, and progressive kyphoscoliosis. Finally, type 4 is associated with short pro-a2(1) chain defect and unstable triple helix and the major features include postnatal fractures, short stature, and moderate skeletal fragility.