Figure 58

Cleavage of the procollagen molecule. Illustration showing the procollagen molecule with N- and C-terminals. Small curved arrows in the upper part of the illustration show where terminals are split from the procollagen molecule to form the collagen (tropocol-lagen) molecule. On the C-terminal of the molecule, the sugar subunit is GlcNac (N-acetylglucosamine) attached to mannose (Man)n. (Adapted from Prockop DJ, et al. N Engl J Med 1979;301:13-23. Copyright © 1979 Massachusetts Medical Society. All rights reserved.)

The important role of collagens in the body can be illustrated by collagenopathies (collagen diseases), which are caused by a deficit or abnormality in the production of specific collagens. Most collagenopathies are attributed to mutations in genes encoding the a chains in the various collagens. In the future, gene therapy could potentially be used either to control deposition of faulty collagen or to reverse the disease process caused by the mutated genes. Table 5.3 lists the most common collagenopathies occurring in humans.

table 5.3. The Most Common Collagenopathies Occurring in Humans

Type of Collagen Disease Symptoms

I Osteogenesis imperfecta Repeated fractures after minor trauma, brittle bones, ab normal teeth, thin skin, weak tendons, blue sclerae, progressive hearing loss

II Kniest dysplasia Short stature, restricted joint mobility, ocular changes leading to blindness, wide metaphyses and joint abnormality seen in radiographs

III Ehlers-Danlos type IV Hypermobility of joints of digits, pale thin skin, severe bruisability, early morbidity and mortality resulting from rupture of vessels and internal organs

IV Alport's syndrome Hematuria resulting from structural changes in the glomerular basement membrane of the kidney, progressive hearing loss, and ocular lesions

VII Kindler's syndrome Severe blistering and scarring of the skin after minor trauma, resulting from absence of anchoring fibrils

IX Multiple epiphyseal dysplasia (MED) Skeletal deformations resulting from impaired endochon dral ossification and premature degenerative joint disease

X Schmid metaphyseal chondrodysplasia Skeletal deformations characterized by modifications of the vertebral bodies and metaphyses of the long bone

XI Stickler's syndrome type II Craniofacial and skeletal deformations, severe myopia, retinal detachment, progressive hearing loss

XVII Generalized atrophic benign epidermolysis Blistering skin disease with mechanically induced dermal-

bullosa (GABEB) epidermal separation, resulting from faulty hemidesmo-

somes, skin atrophy, nail dystrophy, and alopecia

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