Familial tumoral calcinosis (FTC; OMIM 211900) is a severe autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Using linkage analysis, we mapped the gene underlying FTC to 2q24-q31. This region includes the gene GALNT3, which encodes a glycosyltransferase responsible for initiating mucin-type O-glycosylation. Sequence analysis of GALNT3 identified biallelic deleterious mutations in all individuals with FTC, suggesting that defective post-translational modification underlies the disease.We assessed 12 individuals with FTC from two large kindreds of Druze and African-American origin (Fig. 1a) that have been extensively described 1,2 . All affected individuals reported recurrent painful, calcified subcutaneous masses of up to 1 kg (Fig. 1b), often resulting in secondary infection and incapacitating mutilation. Three individuals developed deep periarticular tumors (Fig. 1b), and one succumbed to the disease. All affected individuals had hyperphosphatemia (family 1, 6.2-8.5 mg dl -1 ; family 2, 5.2-6.6 mg dl -1 ) but normal levels of calcium, parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3.With informed consent of all participants, we obtained DNA samples and carried out a genome-wide scan using 362 microsatellite markers (Research Genetics) in family 1. Consanguinity in this kindred allowed us to apply homozygosity mapping to identify in all affected individuals a 15-Mb segment identical by descent, flanked by D2S142 and D2S2284/D2S2177 on 2q24-q31 (Fig. 1). We obtained a maximum multipoint lod score of 6.7 (HOMOZ 3 ). Multipoint linkage analysis in family 2 using seven markers in this critical region further reduced the interval to 3 Mb flanked by D2S111 and D2S1776 (Fig. 1) and yielded a maximum multipoint lod score of 3.4 (GeneHunter 4 ).Using Mapviewer, we identified 11 genes in the 3-Mb region associated with FTC. Of these, B3GALT1, SCN7A, SCN9A, SCN1A and STK39 have roles in neural or neuroendocrine tissues; the functions of TAIP-2, CMYA3, FLJ11457, LOC90643 and LASS6 are mostly unknown. The last positional candidate gene, GALNT3, encodes the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (ppGaNTase-T3; ref. 5). ppGaNTase-T3 belongs to a large family of Golgi-associated biosynthetic enzymes that transfer GalNac from the sugar donor UDP-GalNac to serine and threonine residues and are thereby responsible for initiating O-glycan synthesis, a prevalent form of post-translational modification 6 . RT-PCR analysis showed strong expression of GALNT3 in the skin and kidneys, two tissues of functional relevance to the pathogenesis of FTC 1,2 (Fig. 2a). Using balanced primer pairs, we screened PCR amplicons of all ten coding exons and conserved splice sites of GALNT3 for pathogenic mutations in the genomic DNA of affected individuals (primer pairs and PCR conditions are available on request). Members of the Druze family carried a homozygous G→A transition at position 1524+1 (from the ATG ...

Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

The clinical manifestations of contact allergic dermatitis to dental materials are not uniform. This study was performed to detect the frequent allergens in the dental series associated with contact dermatitis and to define the causal relationship between the different allergens and the relevant clinical presentations. Between the years 2000 and 2004, 134 patients, aged 20-80 years, were patch tested. 121 patients were included in the study. The most frequent oral manifestations were cheilitis and perioral dermatitis (25.6%), burning mouth (15.7%), lichenoid reaction (14.0%), and orofacial granulomatosis (10.7%). 18 (14.9%) patients were dental personnel, all of whom suffered from hand dermatitis. The common allergens detected included goldsodiumthiosulphate (14.0%), nickel sulfate (13.2%), mercury (9.9%), palladium chloride (7.4%), cobalt chloride (5.0%), and 2-hydroxyethyl methacrylate (5.8%). Positive reactions to metals were frequent in all the different clinical variants, and no specific association between a specific clinical presentation and a particular allergen was found. Allergy to mercury was not a significant factor contributing to the pathogenesis of oral lichenoid reactions. However, a strong association with contact allergy to mercury in dental fillings was found in 2 patients with orofacial granulomatosis.

Background Acne vulgaris (acne), a common inflammatory skin disorder, has its peak incidence between 14 and 19 years of age, with girls frequently developing acne earlier than boys. Over recent years, persistent acne is becoming more prevalent in adult women. Objectives This review and panel discussion addresses challenges in acne management, particularly in adult women. The role which nonprescription acne treatment can play is explored when used as monotherapy or as an adjunctive treatment for acne of all severity. Methods The best available evidence on nonprescription acne treatment was coupled with the opinion of an international expert panel of dermatologists to adopt statements and recommendations discussed in this review. Results All severity of acne has a significant burden on patients. Addressing environmental factors that are important for the individual with acne may help to educate, prevent, effectively manage, and maintain acne, as per the panel. They agreed that the adult female acne population has unique needs because of their aging skin and social environment. Nonprescription acne treatment products may help to balance the efficacy and tolerability of prescription acne treatment. Currently, there are no specific guidelines for how to use nonprescription acne treatment products in these patients. Conclusion The panel agreed that guidelines including nonprescription acne treatment either as monotherapy for mild acne or in combination with prescription treatments for more severe acne would address a significant unmet need.

Dowling-Degos disease (DDD; MIM 179850) is a rare autosomal dominant disorder characterized by reticulate flexural hyperpigmentation associated with hyperkeratotic papules, pitted perioral scars and comedo-like lesions or cysts. 1 Characteristic histopathological features include filiform epithelial downgrowths of the rete ridges, typically involving the follicular infundibulum, basilar hyperpigmentation and dermal melanosis. Follicular retention cysts and perivascular mononuclear infiltrates can also be present. 1 Galli-Galli disease is a term that has been used to describe patients displaying prominent acantholytic changes on histology, in addition to clinical and pathological features resembling those of DDD. 2 Two mutations in KRT5, encoding one of the two major basal epidermal keratin intermediate filaments, were recently reported to underlie DDD in a number of European cases. 3 In the present study, we report a novel mutation in KRT5 in a patient with clinical and histopathological features typical of Galli-Galli disease. Case and methods