Dermatosparaxis in a Himalayan Cat: II. Ultrastructural Studies of Dermal Collagen

Abstract

Dermatosparaxis is a connective tissue disease, primarily of sheep and cattle, that results from deficient activity of the NH2-terminal procollagen peptidase. It is characterized by fragile, loose skin that is easily torn with minor trauma. We have identified a cat twith a defect in this procollagen peptidase which affects only a small proportion of the collagen molecules; the majority of the collagen is processed normally. Nonetheless, as seen by transmission and scanning electron microscopy, this population of aberrant collagen molecules significantly alters the structure of individual collagen fibrils, the assembly of fibrils into fiber bundles and the integration of fiber bundles into a normal, woven network in the reticular dermis of skin. Although the clinical findings are less severe than those in sheep and cattle where the enzymatic defect is more complete, the ultrastructural abnormalities are marked and demonstrate that a minority of abnormal collagen molecules cn have a major effect on the structure and function of connective tissues.

Differential ultrastructural aberrations of collagen fibrils in Ehlers-Danlos syndrome types I?IV as a means of diagnostics and classification

“…This makes it difficult to evaluate alterations caused by genetic defects. The literature and our own studies of inherited connective tissue diseases indicate that few morphological changes in collagen fibrils or elastic fibers are unique for a given inherited disease or single genetic defect, as is the case for the hieroglyphic collagen fibrils in animals affected with dermatosparaxis (Holbrook et al 1980). In EDS, the ultrastructural changes are focused on the collagen fibrils, mainly those of the reticular dermis, where they are composed of collagens types I and III for the most part.…”

“…Indeed, EDS VIIa and b were found to be associated with a structural defect of collagen type I (Cole et al 1986;Eyre et al 1985). EDS IV may be caused by mutations of the COL3Algene of collagen type III (Pope et al 1975;Cole et al 1990;Pope 1991); lysyl oxidase deficiency accounts for EDS V (DiFerrante et al 1975), lysyl hydroxylase deficiency for EDS VI (Pinell et al 1972;Wenstrup et al 1989), and procollagen peptidase deficiency for dermatosparaxis in cattle, sheep, and Himalayan cat (Lapiere et al 1971;Fjolstad and Helle 1974;Holbrook et al 1980). Recently, the same procollagen peptidase deficiency, for a long time postulated to exist in humans, was identified in two patients suffering from the analogous EDS type VIIc (Nusgens et al 1992;Smith et al 1992).…”

The natural history, including orofacial features of three patients with Ehlers–Danlos syndrome, dermatosparaxis type (EDS type VIIC)

“…Dermatosparaxis, an autosomal recessive disorder first identified in cattle and subsequently in sheep [Helle and Nes, 1972] and cats [Holbrook et al, 1980], is characterized primarily by extreme fragility of the skin and early death. The corresponding phenotype in humans was first recognized in 1992 in three patients, one of them being the first patient described in this report (patient 1).…”

Collagen Dysplasia (Cutaneous Asthenia) in a Cat

“…17 In the recessive form of the disease, the fibrils and fibers seem to be twisted and do not acquire the cylindrical shape present in normal collagen. 7 This altered conformation is the consequence of a deficiency of the enzyme procollagen terminal peptidase. 3 The second form, which is autosomal dominant, appears in heterozygous individuals as a disorganization of the fibril bundles that compose the altered collagen fibers that are intermingled with collagen fibers of normal conformation.…”