A Novel Mutation of a Leucine Residue in Coil 1A of Keratin 9 in Epidermolytic Palmoplantar Keratoderma

Keratin 9 mutation was examined in a Japanese kindred of epidermolytic palmoplantar keratoderma (EPPK), which is a dominantly inherited autosomal disorder of keratinization characterized by diffuse thickening of the palms and soles and by epidermolytic hyperkeratosis histologically. We report herein a novel mutation, a C → G transversion at nucleotide position 541 that converts a leucine residue (CTC) to a valine (GTC) at codon 159. As in all other reported cases of keratin 9 mutation in EPPK, this mutation lies within the highly conserved coil 1A of the rod domain, which is considered to play a role in the correct alignment of the coiled-coil molecules

Alterations in Synthesis of Various Connective Tissue Components in Werner\u27s Syndrome Cultured Dermal Fibroblasts

Werner\u27s syndrome (WS), a premature aging disorder, is known to have scleroderma-like skin changes. We studied both collagen and glycosaminoglycan (GAG) synthesis in dermal fibroblasts derived from two patients with WS. The total synthesized protein was determined by the incorporation of [3H]-proline, and the synthesized collagen was measured as labeled hydroxyproline. The GAG synthesis was measured by the incorporation of [3H]-glucosamine. The synthesis of total and collagenous protein of fibroblasts from WS was increased about threefold respective to controls. The GAG synthesis of fibroblasts from WS patients was also significantly higher than normal controls. These results suggest that the connective tissue synthesis in WS might be common to be that of scleroderma in the active phase

The Quantitative Changes of the Plasma Fibronectin (FN) with Aging

Using an enzyme linked immunosorbent assay (ELISA), we investigated the changes in the amount of human plasma fibronectin (FN) with aging. The increase of plasma FN concentration with aging was slight up to about 50 years of age. Between 60 and 100 years there was a marked increase of plasma FN concentration with aging. The plasma FN concentration from three patients with Werner\u27s syndrome showed higher value than the average of their age group

Collagen Metabolism in Cutis Laxa Fibroblasts: Increased Collagenase Gene Expression Associated with Unaltered Expression of Type I and Type III Collagen

Collagen metabolism was studied in cutis laxa by analyzing collagen and collagenase gene expression in three dermal fibroblast strains from patients with congenital cutis laxa and comparing them with fibroblasts obtained from age-matched healthy subjects. Normal collagen synthetic activity was observed in the cutis laxa fibroblasts. An increased level of collagenase mRNA and unaltered levels of α1(I) and α1(III) collagen mRNA were found in all cutis laxa cell strains by dot blot hybridization. Reduced levels of elastin mRNA were also detected in these strains. However, no qualitative differences in these mRNA transcripts were detected between the control and cutis laxa fibroblasts by Northern blot analysis. Collagenase activity in fibroblast culture supernatants was then measured using fluorescein isothiocyanate (FITC)-labeled type I collagen. Increased collagenolytic activity in cutis laxa fibroblast culture supernatants was also found. These data suggest that increased collagenase expression of fibroblasts is related to the structural abnormality of dermal connective tissue in cutis laxa