Sx Xiao

Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts

Summary Backgroundu2003Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias caused by mutations in four differentiation‐specific keratin genes. Two major clinical subtypes of PC have been generally recognized. Symmetrically thickened fingernails and toenails are the defining characteristic of PC type 2 (PC‐2) with onset at infancy. Pilosebaceous cysts are the best hallmark of PC‐2, but they usually occur at puberty.

TWEAK/Fn14 Activation Contributes to the Pathogenesis of Bullous Pemphigoid

TWEAK participates in various cellular effects by engaging its receptor of Fn14. Increased levels of soluble TWEAK are associated with systemic autoimmunity in patients with lupus erythematosus, rheumatoid arthritis, or dermatomyositis. However, the role of TWEAK in bullous pemphigoid (BP) remains unknown. In this study, we found an elevated serum level of TWEAK and a positive correlation between serum TWEAK and anti-BP180 antibodies. Immunohistochemistry showed strong TWEAK and Fn14 expression and implied an opposite relationship between the TWEAK and BP180 expression in skin samples from BP patients. Inxa0vitro TWEAK stimuli reduced BP180 expression in HaCaT cells and inhibited the adhesion of cells to the culture dish. Consistently, the transfection of Fn14 small interfering RNA preserved BP180 and protected cells from losing adherence. Moreover, such effect of TWEAK correlated with activation of the extracellular signal-regulated kinase and NF-κB pathways and downstream ADAMs. By silencing ADAM17 with small interfering RNA, we showed that ADAM17 participated in TWEAK-induced BP180 loss. Therefore, TWEAK may contribute to the pathogenesis of BP by reducing BP180 expression and cellular adherence, involving the activation of ERK and NF-κB pathways. TWEAK may serve as a biomarker or therapeutic target of BP.

TWEAK/Fn14 Activation Participates in Ro52-Mediated Photosensitization in Cutaneous Lupus Erythematosus

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) binds to its sole receptor fibroblast growth factor-inducible 14 (Fn14), participating in various inflammatory responses. Recently, TWEAK/Fn14 activation was found prominent in the lesions of cutaneous lupus erythematosus (CLE). This study was designed to further reveal the potential role of this pathway in Ro52-mediated photosensitization. TWEAK, Fn14, and Ro52 were determined in the skin lesions of patients with CLE. Murine keratinocytes received ultraviolet B (UVB) irradiation or plus TWEAK stimulation and underwent detection for Ro52 and proinflammatory cytokines. The chemotaxis of J774.2 macrophages was evaluated on TWEAK stimulation of cocultured keratinocytes. We found that TWEAK, Fn14, and downstream cytokines were highly expressed in CLE lesions that overexpressed Ro52. Moreover, TWEAK enhanced the UVB-induced Ro52 upregulation in murine keratinocytes. Meanwhile, TWEAK stimulation of keratinocytes favored the migration of macrophages through promoting the production of chemokine C–C motif ligands 17 and 22. Furthermore, Fn14 siRNA transfection or nuclear factor-kappa B (NF-κB) inhibitor abrogated the TWEAK enhancement of Ro52 expression in keratinocytes. Similarly, TNF receptor associated factor 2 (TRAF2) siRNA reduced the protein level of Ro52 in these cells upon TWEAK stimulation. Interestingly, UVB irradiation increased the expression of TNF receptor type 1 (TNFR1) but not affecting TNFR2 expression in keratinocytes. In conclusion, the TWEAK/Fn14 signaling participates in Ro52-mediated photosensitization and involves the activation of NF-κB pathway as well as the function of the TRAF2/TNFR partners.

Quality of life in patients with lepromatous leprosy in China

Backgroundu2002 Leprosy has an impact on patients’ quality of life (QoL). However, there has been no study specifically on the impact of the severest type of leprosy‐lepromatous leprosy on QoL.

Two frameshift mutations of the double-stranded RNA-specific adenosine deaminase gene in Chinese pedigrees with dyschromatosis symmetrica hereditaria

Dyschromatosis symmetrica hereditaria (DSH) (also called ‘reticulate acropigmentation of Dohi’ or ‘symmetric dyschromatosis of the extremities’) (MIM 127400) is characterized by a mixture of hyperpigmented and hypopigmented macules and is localized on the back of the hands and feet. Many patients with DSH also have small freckle-like pigmented macules on their faces. The lesions usually appear in infancy or early childhood, commonly stop spreading before adolescence, and last for life. DSH has been reported mainly in Japan, but a similar condition has been reported among Chinese; about 34 pedigrees including 227 cases and two sporadic cases from China have been reported since 1980. Several cases of DSH have been reported among Koreans, Indians, Europeans and South Americans. No racial difference in the condition has been observed, but the disorder might be distributed mainly in East Asia. The DSH locus has been mapped to chromosome 1q21 and then, in 2003, pathogenic mutations were identified in the double-stranded RNA-specific adenosine deaminase (DSRAD) gene. DSRAD spans 30 kb and contains 15 exons. It encodes RNA-specific adenosine deaminase composed of 1226 amino acid residues, with a calculated molecular mass of 139 kDa. In this study, we performed mutation detection of the DSRAD gene in two typical Chinese families with DSH in which two heterozygous mutations were identified.

Rasch analysis holds no brief for the use of the Dermatology Life Quality Index (DLQI) in Chinese neurodermatitis patients

BackgroundThe Dermatology Life Quality Index (DLQI) is the most widely used measure of health-related quality of life (HRQoL) associated with skin disease. Recently, the psychometric properties of the DLQI have caused some controversy because the instrument appears not to meet the requirements of modern test theory. The purpose of this study was to assess whether these psychometric issues also occur in Chinese patients with neurodermatitis.MethodsOne hundred fifty consecutive outpatients (83 males and 67 females) seeking treatment for neurodermatitis were assessed for eligibility for this prospective study between July 1, 2011 and September 30, 2011. The DLQI and a demographic questionnaire were completed. One female participant who incompletely answered the DLQI was excluded. Data were analyzed using the Rasch model in order to obtain meaningful scores for the DLQI. Scale assessment included analysis of rating scale function, item fit to the Rasch model, aspects of person-response validity, unidimensionality, person-separation reliability, and differential item function.ResultsThe rating scale advanced monotonically for all items in the DLQI, but item 9 did not demonstrate acceptable goodness-of-fit (Infit MnSq values >1.3) to the Rasch model. The 10 items of the DLQI met the criteria for person-separation reliability (PSIu2009=u20092.38) and the first latent dimension (general QoL) accounted for 50.8xa0% of the variance; but the variance explained by the second dimension (7.1xa0%) exceeded the criterion of 5xa0%. There were also limitations related to person-response validity, becauseu2009≥u20095xa0% (18.1xa0%) of cases demonstrated unacceptable fit. There was no uniform differential item functioning.ConclusionsFor neurodermatitis patients, the DLQI seems to have poor fit to the Rasch model; therefore, we recommend against using this instrument with neurodermatitis patients.

A novel mutation of CYLD in a Chinese family with multiple familial trichoepithelioma.

Backgroundu2002 Trichoepithelioma is a benign cutaneous tumour that originates from hair follicles and occurs either as a sporadic non‐familial or a multiple‐familial type. Recently, several mutations in the cylindromatosis (CYLD) gene have been reported in multiple familial trichoepithelioma (MFT).

TWEAK/Fn14 Activation Participates in Skin Inflammation

Tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) participates in multiple biological activities via binding to its sole receptor—fibroblast growth factor-inducible 14 (Fn14). The TWEAK/Fn14 signaling pathway is activated in skin inflammation and modulates the inflammatory responses of keratinocytes by activating nuclear factor-κB signals and enhancing the production of several cytokines, including interleukins, monocyte chemotactic protein-1, RANTES (regulated on activation, normal T cell expressed and secreted), and interferon gamma-induced protein 10. Mild or transient TWEAK/Fn14 activation contributes to tissular repair and regeneration while excessive or persistent TWEAK/Fn14 signals may lead to severe inflammatory infiltration and tissue damage. TWEAK also regulates cell fate of keratinocytes, involving the function of Fn14-TNF receptor-associated factor-TNF receptor axis. By recruiting inflammatory cells, promoting cytokine production, and regulating cell fate, TWEAK/Fn14 activation plays a pivotal role in the pathogenesis of various skin disorders, such as psoriasis, atopic dermatitis, cutaneous vasculitis, human papillomavirus infection and related skin tumors, and cutaneous autoimmune diseases. Therefore, the TWEAK/Fn14 pathway may be a potential target for the development of novel therapeutics for skin inflammatory diseases.

A novel splicing mutation and haplotype analysis of the FECH gene in a Chinese family with erythropoietic protoporphyria

Backgroundu2002 Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of haeme biosynthesis resulting from a partial decrease in ferrochelatase (FECH) activity leading to excessive accumulation of protoporphyrin. Clinical manifestation normally requires coinheritance of a common hypomorphic FECH allele and a deleterious FECH mutation.

Novel frameshift mutation of the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria

© 2008 The Authors 1375 JEADV 2008, 22, 1365–1401 Journal compilation