Deficiency of the core proteins of dermatan sulphate proteoglycans in a variant form of Ehlers‐Danlos syndrome

Abstract

A variant form of Ehlers-Danlos syndrome with single adrenocorticotrophic hormone (ACTH) deficiency and mild diabetes mellitus was studied by immunohistochemical and biochemical analyses of the connective tissue. The patient exhibited features characteristic of the Ehlers-Danlos syndrome, such as fragility, hyperextensibility, and bruisability of the skin and large veins were readily seen, but no hypermobility of any joint was detectable. Biochemical studies of the connective tissue confirmed that the apparent synthesis of collagens was within normal limits, but the deposition of the major proteoglycan in the skin of this patient was markedly reduced, mainly because the synthesis of core protein of dermatan sulphate proteoglycan was defective.

A Role for Decorin in the Structural Organization of Periodontal Ligament

“…This hypothesis is supported by findings that in growth hormone-deficient rats delayed and disturbed development of teeth and jaws is associated with decreased expression of decorin (Zhang et al, 1995). Deficient decorin expression by fibroblasts has also been reported in certain inherited disorders, including osteogenesis imperfecta, infantile progeroid syndrome, and in Ehlers-Danlos syndrome (EDS) (Beavan et al, 1993;Fedarko et al, 1992;Fushimi et al, 1989). In addition to several systemic defects, patients suffering from osteogenesis imperfecta, infantile progeroid syndrome, or EDS types I and VIII also have abnormalities in development and eruption of teeth (Pope et al, 1992;Yu and Zeng, 1991).…”

“…Although glycoproteins and proteoglycans regulate collagen fibrillogenesis, it is not known whether these disorders also involve defects in molecules other than collagen. Interestingly, EDS types IV, VII, VIII, and IX, which involve defective collagen fibrillogenesis as one of their main characteristics, are also associated with early onset periodontal disease (Aldred and Bartold, 1998;Fushimi et al, 1989;Hartsfield and Kousseff, 1990;Ooshima et al, 1990). In EDS type IV, the basic defect seems to be mutations in the COL3A1 gene, whereas EDS type VII involves mutations in COL1A1 or COL1A2 genes.…”

Age-related Changes in the Proteoglycans of Human Skin

“…For example, the small proteoglycan decorin binds to type I collagen (18,19), and targeted disruption of decorin results in aberrant collagen fibrils and in a reduction in the tensile strength of skin (20). Similarly, a patient with a variant form of Ehlers-Danlos syndrome was found to have a substantially reduced amount of dermal decorin (21). Previous work has shown that decorin and versican are the major proteoglycans extracted from human skin (16).…”

Le syndrome d’Ehlers-Danlos : l’architecture matricielle en question

“…Ces observations suggèrent une participation de ces deux protéoglycanes à la physiopathogénie du syndrome d'Ehlers-Danlos chez l'homme. Les souris transgéniques, dont le gène codant pour la décorine a été invalidé, ont une peau fragile avec une capacité d'extension réduite [30], ce que confirment des données recueillies dans deux cas isolés d'EDS, pour lesquels des altérations de la synthèse de protéoglycane à dermatane sulfate, et notamment de décorine, ont été décrites [31,32]. Un phénotype avec des manifestations cutanées, mais surtout articulaires, proche de l'EDS classique, est observé chez les souris dont le gène codant pour la thrombospondine-2 (TSP-2) a été invalidé [33].…”