The present data confirm the genetic basis of the combined DDD-HS phenotype and suggest that Notch signalling may play a central role in the pathogenesis of this rare condition.

Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs), the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR) protein, whose function is poorly understood. TSPEAR knock-down resulted in altered expression of genes known to be regulated by NOTCH and to be involved in murine hair and tooth development. Pathway analysis confirmed that down-regulation of TSPEAR in keratinocytes is likely to affect Notch signaling. Accordingly, using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter. Collectively, these observations indicate that TSPEAR plays a critical, previously unrecognized role in human tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.

Cochrane Database of Systematic Reviews penicillin and one erythromycin), which was compared to either no treatment or placebo, and one trial used selenium compared to physiological salt solution. Treatments lasted from six to 18 months.The most common setting was the hospital, and two studies were multicentre. The studies were conducted in the UK, Sweden, Tunisia, Israel, and Austria. There was a small number of previous episodes of cellulitis in those recruited to the trials, ranging between one and four episodes in each study. The antibiotic trials assessed prevention with antibiotics in people with cellulitis of the legs, and the selenium trial assessed people with cellulitis of the arms. Key resultsOur main outcome was prevention of repeated episodes of cellulitis. Our other outcomes included the number of repeated attacks of cellulitis, time to next attack, hospitalisation, quality of life, development of antibiotic resistance, adverse reactions and death.Combining the results of all five trials that used antibiotics, we found moderate-certainty evidence that for those people under preventative treatment, antibiotic treatment in general, and penicillin in particular, is probably both e ective and safe for the prevention of repeated episodes of leg cellulitis when compared with no treatment or placebo. Interventions for the prevention of recurrent erysipelas and cellulitis (Review)