This thesis is dedicated to my grandparents

proteoglycans
Proteoglycans are build out of a protein core to which short oligosaccharides and longer
chains of glycosaminoglycans (GAGs) are covalently attached. There is a large variety of
proteoglycans based on the types and lengths of GAGs as well as the sequence and length of the
protein core. Chondroitin sulfate, keratan sulfate, heparin sulfate, and dermatan sulfate are four
different forms of GAGs that consist of repeating disaccharide units. The sulfates present on the
GAGs create a highly negatively charged environment that is hydrophilic. Thus, connective
tissues that contain large amounts of proteoglycans will also contain relatively large amounts of
water bound to the proteoglycans. In addition to water, proteoglycans bind cationic proteins,
which in some cases include growth factors, resulting in a mechanism by which tissues can store
growth factors in the matrix.
The size of these proteoglycans can vary significantly. Aggrecan, predominantly found in
cartilage is a very large protein (molecular weight of more than 200,000 kDa), while decorin,
biglycan, fibromodulin, and lumican are small proteoglycans (30 to 60 kDa). The latter interact
with collagen and function to regulate the formation of collagen fibrils and help stabilize the
collagen network. Although their functions are not completely understood, they likely have other
roles based on their ability to bind other matrix molecules such as elastin and fibronectin and on
their affinity for growth factors.
c/ glycoproteins
Along with the proteoglycans, the many other noncollagenous matrix glycoproteins
found in connective tissues form much of what is sometimes described in histological terms as
the "ground substance". This rather inert-sounding description should in no way be taken to
suggest that these matrix components simply fill in or hold the tissue together. Rather these
proteins participate actively in creating the information-rich environment described earlier.
Proteins in this group include fibronectin, vitronectin, osteopontin, laminin, and thrombospondin.
Fibronectin is found in most connective tissues throughout the body. Laminin is particularly
prominent in basement membranes, and osteopontin is found in greater amounts in cartilage and
bone. All of these proteins bind to cells through specific cell-surface receptors to promote
attachment of cells to the matrix. The proteins also interact with the other matrix proteins to
further integrate the cells with the extracellular matrix. Through these interactions, they function in
regulating tissue morphogenesis as well as tissue repair and remodelling. They also appear to
play a role in other diverse processes, including tumour growth and metastasis.
1.2.2 Connective tissue disorders (CTD)
Heritable disorders that involve connective tissue are among the most common genetic
diseases in humans. The first comprehensive effort to classify these diseases was made by
Victor McKusick in a series of reports and then in the monograph Heritable Disorders of
Connective Tissue. Based on pattern of inheritance, the cluster of signs and symptoms, the
histological changes in tissues and limited information about the molecular defects involved, he
drew the first classification of CTD. In the advent of molecular genetics, some limitations of
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