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AIM: To investigate the application of rapid diagnosis and classification of retinal artery occlusion(RAO)by multicolor imaging(MCI)with optical coherence tomography(OCT).METHODS: Totally 19 patients(19 eyes)who were diagnosed with RAO in our hospital were retrospectively analyzed. All of the patients were diagnosed of RAO after ophthalmologic examination, including 13 eyes of central retinal artery occlusion(CRAO), 5 eyes of branch retinal artery occlusion(BRVO)and 1 eye of RAO with sparing of cilioretinal artery. The best corrected visual acuity, slit lamp, OCT, MCI, FFA and visual field were performed on the patients, and the examination results and image data were analyzed.RESULTS: Totally 12(63%)eyes showed dullness or disappearance of pupil response to light, 16(84%)eyes showed total or partial paleness and edema in the posterior pole of retina, and 10(53%)eyes showed narrowing of retinal artery by slit-lamp examination. FFA examination was performed in 10 cases(53%). However 9 cases were not examined, including 6 cases with serious systemic diseases, 2 cases rejecting to be checked and 1 case with drug allergy. All the patients showed specific manifestations in both MCI and OCT examination, and the typical highly reflectivity of inner retinal layers in OCT formed tight one-to-one relationship with the green ischemic area in MCI.CONCLUSION: RAO can be diagnosed quickly by MCI combined with OCT, and their image characteristics can accurately identify the retinal ischemic areas, which can help for disease classification and prognosis.

SHANK‑associated RH domain‑interacting protein (SHARPIN) is a component of the linear ubiquitin chain assembly complex that can enhance the NF‑κB and JNK signaling pathways, acting as a tumor‑associated protein in a variety of cancer types. The present study investigated the role of SHARPIN in cutaneous basal cell carcinoma (BCC). Human BCC (n=26) and normal skin (n=5) tissues, and BCC (TE354.T) and normal skin (HaCaT) cell lines were used to evaluate SHARPIN expression level using immunohistochemistry and western blotting, respectively. A lentivirus carrying SHARPIN‑targeting or negative control short hairpin RNA was infected into TE354.T cells, and the infected stable cells were assayed to analyze tumor cell proliferation, cell cycle, apoptosis, migration and invasion by Cell Counting Kit‑8 and 5‑ethynyl‑2'‑deoxyuridine incorporation assays, flow cytometry and Transwell assays. Western blotting was performed to assess the protein expression levels of gene signaling in SHARPIN‑silenced BCC cells. SHARPIN protein expression levels were downregulated or absent in BCC cancer nests and precancerous lesions compared with normal skin samples. In addition, SHARPIN expression levels were lower in TE354.T cells compared with HaCaT cells. SHARPIN shRNA enhanced tumor cell proliferation and the S phase of the cell cycle, whereas BCC cell apoptotic rates, and migratory and invasive abilities were not significantly altered. The expression levels of cyclin D1, cyclin‑dependent kinase 4, phosphorylated‑c‑JUN and GLI family zinc finger 2 proteins were increased, whereas Patched 1 (PTCH1) and PTCH2 were decreased in the SHARPIN‑shRNA‑infected BCC cells. Therefore, the present results suggested that SHARPIN may act as a tumor suppressor during BCC development.

Posterior capsular opacification(PCO)is the most common complication that leads to loss of vision after cataract surgery. Neodymium doped: Yttrium-Aluminum-Garnet(Nd:Yag)laser capsulotomy is a common treatment for PCO, but still associated with several complications. In the past decades, the prevention and treatment of PCO have always been a hot spot of research in ophthalmology. This review will address the advances in the prevention and treatment of PCO in the aspects of surgical techniques and types of intraocular lens(IOL).

Aim To investigate the role of cAMP response element-binding protein (CREB) in the regulation of odonto/osteogenic differentiation of stem cells from the apical papilla (SCAPs). Methodology Stem cells from the apical papilla were obtained from human impacted third molars (n = 15). Isolated SCAPs were transfected with CREB overexpressing/silenced lentivirus. Transfected cells were stained with alizarin red to investigate mineralized nodule formation. The expression of the mineralization-related genes, alkaline phosphatase (ALP), collagen type I (Col I), runt-related transcription factor 2 (RUNX2), osterix (OSX) and osteocalcin (OCN), was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Protein expression of the odontogenic-related marker dentine sialoprotein (DSP) and the osteogenic-related marker RUNX2 was measured by Western blotting analysis. One-way analysis of variance (anova) and Student's t-test were used for statistical analysis (a = 0.05). Results The overexpression of CREB enhanced mineralized nodule formation and up-regulated (P

Objectives: To investigate molecular mechanisms of nicastrin (NCSTN) mutations inducing acne inversa (AI). Methods: New and old lesional and non-lesional skin samples were obtained from an AI patient. Healthy skin samples were obtained from the buttocks of 100 non-AI patients. Hematoxylin-eosin staining and immunohistochemistry of NCSTN protein were examined. All exon-intron and exon boundary sequences were polymerase chain reaction (PCR) -amplified and sequenced. Bioinformatic analyses of NCSTN 3’-untranslated regions (3’UTR) were conducted using RegRNA2.0. 3’UTR of NCSTN was cloned vector of psiCHECK-2 vector; the mutant 3’UTR NCSTN-psiCHECK-2 was constructed on a template of NCSTN 3’UTR. A dual-luciferase reporter gene assay, real-time reverse transcription (qRT)-PCR and Western blot analysis were conducted to evaluate functional changes associated with the mutation. Results: We identified a novel deletion mutation of the NCSTN gene in the NCSTN 3’UTR region (designated c.2584-2585del CA) at the binding site of human micro-RNA-155 (hsa-miR-155). Levels of NCSTN protein were potently lower in epidermis and hair follicles of AI patients with lesions than in healthy skin. The hsa-miR-155+mutant NCSTN significantly downregulated in dual luciferase assay, qRT-PCR, and Western blot. The novel deletion mutation was confirmed to be a pathological cause of AI. Conclusions: miR-155 downregulates the expression of NCSTN by binding NCSTN 3’UTR, providing a possible new mechanism of loss of NCSTN function in AI patients. hsa-miR-155 functions as a promoter in AI, and is a potential therapy target for AI.

Aiming at the problem of the algorithm of target recognition based on SIFT(Scale invariant feature transform) feature matching is poor at celerity and the algorithm of target tracking based on the target's color feature is easily affected by outside. A target recognition algorithm based on SIFT which based on color guide and a target tracking algorithms based on compressed sensing theory is presented. According to the color image information such as pre-preprocessing identification, identification of the target region, Obtained according to pretarget template, after recognition of the pre-image for SIFT feature matching, can be more accurately identify the target, and determines the target pixel coordinates in the image according to the determined target pixel coordinate. Used compressed sensing target tracking algorithm, you can target the implementation of tracking. The experiments prove that these two algorithms can be applied to panoramic visual object recognition and tracking.

This paper presents an improved method based on Speed up Robust Features (SURF) algorithm to achieve fast image stitching. As the variability of scenes lead to instability of features, expecting to obtain accurate number of features is pretty difficult and time-consuming. support vector machine (SVM) applied in this paper to predict primary threshold of determinant of Hessian matrix can conspicuously reduce detected feature points and simplify the process of features matching. This paper also combines an optimized method of image preprocessing-cylindrical projection and image interpolation to weigh the final quality of stitching image and stitching time. Several experiments are conducted to verify the performance of improved SURF.

A total of 1224 Neisseria gonorrhoeae isolates from Guangzhou in 2 periods (2000-2005 and 2008-2013) were subjected to antimicrobial susceptibility testing. The percentage of penicillin- and ciprofloxacin-resistant isolates increased from 71.1% (473/665) to 90.9% (508/559) and 88.9% (591/665) to 98.0% (548/559), respectively. All isolates remain susceptible to spectinomycin and ceftriaxone, with increasing minimum inhibitory concentrations.

After a coal mine disaster, especially a gas and coal dust explosion, the space-restricted and unstructured underground terrain and explosive gas require coal mine rescue robots with good obstacle-surmounting performance. This paper tackles path-planning or collision avoidance problem. The collision avoidance problem in path planning of mobile robots was inspired from fuzzy control concept. The deduction of the path-planning algorithm is followed. Fuzzy rules and fuzzy inference based on experiences is built, it constructed a reasonable and applicable control reactive rule table. The simulation results are presented to validate the approach. And it is also proved that the control arithmetic is available in both static and dynamic obstacles in coal mine environment.

Conventional PID controllers are widely used in fin stabilizer control systems, but they have time-variations, nonlinearity, and uncertainty influencing their control effects. A lift feedback fuzzy-PID control method was developed to better deal with these problems, and this lift feedback fin stabilizer system was simulated under different sea condition. Test results showed the system has better anti-rolling performance than traditional fin-angle PID control systems.

Hailey-Hailey disease (HHD) is an autosomal dominant skin disorder characterized by recurrent eruption of vesicles and bullae at the sites of friction and in the intertriginous areas. Mutations in the ATP2C1 gene encoding the human secretory pathway calcium ATPase 1 (hSPCA1) have been identified as the causative mutations in HHD. In this study, we used direct sequencing and restriction endonuclease digestion to analyze mutations of the ATP2C1 gene in a Chinese three-generation pedigree. A heterozygous T-to-C transition at nucleotide 1004 in exon 12 of ATP2C1 gene was detected. After summarizing the reported cases with ATP2C1 mutation, we concluded that the T1004C transition resulted in a novel missense mutation of leucine condon (CTG) to proline (CCG) at amino acid residue 335(L335P) in hSPCA1. Here, a genetic diagnosis was made for the proband's daughter before the clinical presentation. The study realized the molecular diagnosis in the HHD pedigree. Our findings should be useful for genetic counseling and prenatal diagnosis for the affected family and in demonstrating the critical role of the ATP2C1 gene in the pathogenesis of HHD further.

Vitiligo is an acquired depigmentation disorder of the skin and hair caused by the selective destruction of melanocytes from the epidermis that gives rise to well-defined depigmented patches. Strong genetic predisposition has been well recognized. Previous reports have described five significant vitiligo susceptibility loci spread over five different chromosomes, 1p31 (AIS1), 7q (AIS2), 8p (AIS3), 4q13-q21 (AIS4), and 17p (SLEV1). In addition, our previous genome-wide scan of 106 Chinese vitiligo families presented suggestive linkages on five additional chromosome segments, 1p36, 6p21-p22, 6q24-q25, 14q12-q13, and 22q12. To clarify the significance of these suggestive loci, we have now extended this study to a total of 143 Chinese vitiligo families and increased the marker density. Two linkage signals on 6p21-p22 and 22q12 that were previously only suggestive now meet genome-wide criteria for significant linkage, establishing their importance as major vitiligo susceptibility loci. Linkage signals on 1p36 and 6q24-q25 did not improve our previous findings, but on 14q showed negative in the 143 family cohorts. The results presented here further demonstrate the genetic complexity of vitiligo pathogenesis and point to new chromosomal locations for further research to identify the specific genes involved in this process.

Objectives Psoriasis is common in childhood. The aim of this study was to present the clinical and epidemiological profile of childhood psoriasis in China. Methods A total of 277 childhood psoriasis patients younger than 16 years old were enrolled. Statistical analysis and heritability were performed using EPI INFO 6.0, spss 10.0 and Falconer's method. Results The median age was 11 years. The male : female ratio was 1 : 1.13. The median age of onset was 10 years. Of the patients, 48.7% had previous episodes of psoriasis. Of the 277 children with psoriasis, 68.6% had plaque-type psoriasis, 28.9% had guttate psoriasis, 1.1% presented pustular forms of psoriasis and 1.4% had erythroderma. The extensor surface of the extremities was the most frequently affected site in our patients, followed by the appearance of lesions on the scalp. A positive family history of psoriasis was found in 34.3% patients. The prevalence of psoriasis in first- and second-degree relatives was 7.0% and 1.0%, respectively. The heritability of psoriasis in first- and second-degree relatives was 72.67% and 55.18%, respectively. Conclusion Our epidemiologic studies offer the information about Han Chinese distribution, which provide clues to describe psoriasis in children.

HLA-Cw6 is strongly associated with psoriasis and has been suggested to be the PSORS1 gene that confers susceptibility to early-onset psoriasis. In this study of the clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population, we typed HLA-C in a cohort of 679 patients and compared the two groups. Cw*0602-positive patients (n=345) had an earlier disease onset (p < 1 x 10(-5)), more severe disease (p < 1 x 10(-3)), higher frequency of guttate psoriasis (p < 1 x 10(-9)), more affected legs and trunk (p < 1 x 10(-5)), higher incidence of Kobner's phenomenon (p=0.005) and of trauma history (p=0.009). Cw*0602-negative patients (n= 334) had more palmoplantar pustulosis (p=0.004), nail changes (p=0.001) and scalp involvement (p=0.007). However, there was no statistically significant difference between the two groups regarding age, gender, incidence of plaque psoriasis, erythrodermic, inverse, psoriatic arthritis, and the precipitation factors stress and infection. The study showed that Cw*0602-positive patients had some obvious clinical differences from Cw*0602-negative patients in a Han Chinese population, which provides evidence for an HLA-Cw*0602-associated phenotype in psoriasis.

Background Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Complement component 4 (C4) has be proved to play a role in pathogenesis of SLE. In the present study, we investigated the effect of C4 on T cells differentiation. Methods Thirty SLE patients were included in this study. CD4+ T cells were isolated from healthy subjects, and dendritic cells (DCs) were isolated from healthy subjects or SLE patients. C4 was supplemented to co-incubate with T cells and DCs. Results Serum C4 concentration was positively correlated with regulatory T cell (Treg) percentage (R2 = 0.5907, p

Brooke–Spiegler syndrome (BSS) is an autosomal dominant disease characterized by cylindromas, trichoepitheliomas and occasionally spiradenomas. The disease gene was mapped to 16q12-13, and mutations in the CYLD gene were identified in families with BSS. In the present report, we describe a large consanguineous Chinese family with BSS showing an intra-family phenotypic variability. Clinically, some affected individuals only revealed discrete small skin-coloured tumors whereas the proband showed an expansion of multiple large tumors on the back of nose and numerous dome-shaped papules on her scalp. Histologically, both trichoepitheliomas and cylindromas were found in the affected individuals. By sequence analysis, we identified a recurrent mutation 2272C>T (R758X) of the CYLD gene in the affected individuals of this family, which was previously identified in other ethnic families with familial cylindromatosis. Our result provided additional information for phenotype–genotype correlation in BSS.

Our purpose was to explore potential genetic models for systemic lupus erythematosus (SLE) and analyze genetic epidemiologic characteristics of SLE in a Chinese population. Data for 695 patients with SLE were obtained by using a uniform questionnaire. Patients, clinical characteristics and their family history were analyzed using software. A complex segregation analysis was conducted to propose potential genetic models for SLE. The mean +/- SD age of onset were 30.2 +/- 10.5 years and mean time to progression to SLE was 32.5 +/- 44.4 months. The most frequent initial manifestations were malar rash (61.3%). During the evolution of the disease, the main clinical features were arthritis in 73.6% of our patients, followed by malar rash (68.1%), and renal involvement (56.7%). As the first symptom, the late-onset group (onset of disease beyond the age of 50 years) less often showed malar rash (45% vs. 63.4% in the early-onset group; p = 0.001). There were no significant differences in the other cumulative clinical symptoms between late-onset and early-onset group, except for a lower prevalence of malar rash, photosensitivity and alopecia and a higher prevalence of mucosal ulcers in the late-onset group. A positive family history of SLE was obtained in 50 patients (7.2%). There were no statistical differences in clinical characteristics between familial SLE and sporadic SLE patients. The heritability of SLE was 43.6%, the genetic model of SLE could be polygenetic model and major gene mode is the best fitted one. SLE could be a multifactorial disease with polygenetic model.

Background Some studies have shown discrepancies in human leucocyte antigen (HLA) associated with alopecia areata (AA) between different ethnic populations. Objective To investigate whether HLA-I, -DQA1 and -DQB1 alleles and the HLA haplotype are associated with AA, and the correlation between the HLA haplotype profile, age of onset and severity of AA in Chinese Hans. Methods The polymerase chain reaction-sequence specific primer (PCR-SSP) method was used to analyse the frequencies of HLA class I, -DQA1 and -DQB1 alleles in 192 patients with AA and 252 controls in Chinese Hans. The linkage disequilibrium was calculated using the 2 × 2 table. Results The 24 two-locus haplotypes [including A*02-B*18, A*02-B*27, A*02-B*52, A*02-Cw*0704, A*02-DQA1*0104, A*02-DQB1*0604, A*02-DQB1*0606, B*18-Cw*0704, B*18-DQA1*0104, B*18-DQA1*0302, B*18-DQB1*0606, B*27-Cw*0704, B*27-DQA1*0104, B*27-DQA1*0302, B*52-Cw*0704, B*52-DQA1*0104, B*52-DQA1*0302, B52-DQB1*0606, Cw*0704-DQA1*0104, Cw*0704-DQA1*0302, Cw*0704-DQB1*0606, DQA1*0104-DQB1*0604, DQA1*0104-DQB1*0606, DQA1*0302-DQB1*0606 (P

Background Serological typing of the human leucocyte antigen (HLA) has shown discrepancies in HLA associations with vitiligo in different ethnic populations. Objective To evaluate the distributions of HLA at class I and II loci that may contribute to the genetic susceptibility of vitiligo patients in Chinese Hans population. Methods We analysed the allelic frequencies of HLA class I and II by using the polymerase chain reaction sequence-specific primer (PCR-SSP) method in 187 patients with vitiligo and 273 controls in Chinese Hans. The linkage disequilibrium was calculated from a 2 × 2 table. Results Two-locus haplotypes including HLA-A25-B13, HLA-A25-B27, HLA-A25-Cw*0602, HLA-A25-DQA1*0302, HLA-A25-DQA1*0601, HLA-A25-DQB1*0303, HLA-B13-Cw*0602, HLA-B13-DQA1*0302, HLA-B13-DQA1*0601, HLA-B27-Cw*0602, HLA-B27-DQA1*0302, HLA-B27-DQA1*0601, HLA-B27-DQB1*0303, HLA-B27-DQB1*0503, HLA-Cw*0602-DQA1*0302, HLA-Cw*0602-DQA1*0601, HLA-Cw*0602-DQB1*0303, HLA-Cw*0602-DQB1*0503 and HLA-DQA1*0302-DQB1*0503 were associated with all types of vitiligo in Chinese Hans. The extended haplotypes HLA-A25-B13-Cw*0602, HLA-A25-B27-Cw*0602, HLA-DQA1*0302-DQB1*0303-Cw*0602 and HLA-B13-DQB1*0303-Cw*0602 were found to be associated with all types of vitiligo in Chinese Hans, whereas the frequency of HLA-A25-Cw*0602-DQA1*0302 was significantly increased in generalized vitiligo but not in localized vitiligo. The frequencies of HLA-A25-DQA1*0302-DQB1*0503 and HLA-A30-DQA1*0302-DQB1*0303 were higher in childhood vitiligo than in adult vitiligo, and the frequency of HLA-A25-B13-DQB1*0303-Cw*0602 was shown to be associated with adult vitiligo but not childhood vitiligo. Conclusion This study demonstrates not only the differential association between HLA markers and types of vitiligo according to distribution or age at onset but also newly found high-risk haplotypes in Chinese vitiligo patients.

To study the clinical and epidemiologic profile of childhood alopecia areata, we performed a survey in which a total of 226 childhood patients less than 16 years old were enrolled. Statistical analysis and herita- bility were performed using EPI INFO 6.0, SPSS10.0, and the Falconer method. The median age of onset was 10 years. The majority of patients (84.96%) pre- sented with limited alopecia. The male : female ratio was 1.4:1. Boys appeared to have more severe involvement. The earlier the age of onset, the greater the severity of the disease. Sixty-seven patients (29.65%) had previous epi- sodes of alopecia areata. Greater severity and longer duration were seen in the relapsing patients than in the primary patients. Six patients (2.65%) had an associated disease. A positive family history was reported in 25 patients (11.06%). The prevalence figures for alopecia areata in first-, second-, and third-degree relatives of the probands were 2.87%, 0.40%, and 0.13%, respec- tively. The heritabilities of AA in first-, second-, and third-degree relatives were 51.20%, 46.25%, and 25.65%, respectively. It can be speculated that the effect of genetic factors is important in the occurrence of this disease. Alopecia areata (AA) usually presents as a sudden onset of patchy, nonscarring hair loss. It is hypothesized to be an organ-specific autoimmune disease with genetic predisposition and an environmental trigger (1). This disease affects both adults and children. We have done a survey of the genetic epidemiology of 1032 patients with AA and concluded that the effect of genetic factors is strong (2). There are limited data on childhood AA (3-5). There are no reports of a large cohort of Chinese children with AA. The purpose of our study was to review the epidemiology, clinical aspects, and complications of AA in Chinese patients less than 16 years old.

Background Vitiligo is an acquired depigmentary disorder of the skin and hair which results from selective destruction of melanocytes. Serological typing and genotyping of human leukocyte antigen (HLA) have shown discrepancies in HLA associations with vitiligo in different ethnic populations. Methods Polymerase chain reaction sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA 1 and -DQB 1 alleles among 187 patients with vitiligo and 273 healthy controls through Epi Info version 6 package (Centers for Disease Control and Prevention, Atlanta, GA, USA). Results The frequencies of HLA-DQA1 *0302 (OR = 1.98, P c < 0.01), -DQB1 *0303 (OR = 3.14, P c < 0.001), and -DQB1*0503 (OR = 3.36, P c < 0.05) alleles were significantly increased in patients with vitiligo compared with controls, and HLA-DQA 1 *0501 (OR = 0.40, P c < 0.01) allele frequency was highly decreased. HLA-DQA1 *0302 (OR = 5.19, P c < 0.001), -DQA1*0601 (OR = 2.95, P c < 0.05), -DQB1 *0303 (OR = 4.50, P c < 0.001), and -DQB1 *0503 (OR = 6.69, P c < 0.001) alleles were positively associated, whereas HLA-DQA1*0501 (OR = 0.05, P c < 0.001) allele was negatively associated with childhood vitiligo patients, and HLA-DQB1*0303 (OR = 2.76, P c < 0.001) allele was positively associated with adult vitiligo patients compared with controls. The frequency of HLA-DQB1*0303 (OR = 3.72, P c < 0.001) allele was significantly increased in localized vitiligo patients vs. controls, whereas HLA-DQA1*0302 (OR = 2.47, P c < 0.01), -DQB1 *0303 (OR = 2.67, P c < 0.01), and -DQB1 *0503 (OR = 4.46, P c < 0.01) allele frequencies were significantly increased and -DQA1 *0501 (OR = 0.27, P c < 0.01) allele frequency was highly decreased in generalized vitiligo patients. Conclusions HLA-DQA1 *0302, -DQA1*0601, -DQB1 *0303, and -DQB1 *0503 alleles could be susceptible alleles of vitiligo, while HLA-DQA1*0501 allele could be a protective allele in Chinese Hans. There may be different genetic backgrounds between vitiligo patients of childhood and adult, localized and generalized.

Accumulative evidences have shown that certain HLA loci are associated with alopecia areata (AA), but with existing differences in ethnic distribution. No report has ever been published about this in Chinese Hans. To investigate whether HLA-DQA1 and DQB1 alleles are associated with AA, and the correlation of the HLA profile with age of onset, severity, duration of current attack, recurrence and family history of AA in Chinese Hans. The polymerase chain reaction–sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA1 and DQB1 alleles in 192 patients with AA and 273 healthy controls in Chinese Hans. The significant increased frequencies of HLA-DQA1*0104 (OR=3.38, P c

Multiple familial trichoepithelioma (MFT) is an autosomal dominant skin disease characterized by the presence of many small benign tumors with pilar differentiation predominantly on the face. The first locus has been previously mapped to chromosome 9p21, but no gene for MFT has been identified to date. To identify the disease gene in a large Chinese family, we initially performed linkage analysis with microsatellite markers from 9p21, but failed to confirm the linkage to this region. Previous publications showed MFT and familial cylindromatosis (FC) can occur within one family and in a single person. Therefore, we speculated that the cylindromatosis gene (CYLDI gene) responsible for FC may be related to the pathogenesis of MFT. In view of that, we genotyped all available individuals using 11 microsatellite markers spanning the CYLDI gene region at 16q12-q13. We identified the linkage of MFT to this region. Mutation analysis in the CYLDI gene detected a frameshift mutation, designated as c.2355-2358delCAGA. The study firstly identified the cylindromatosis gene responsible for MFT and showed that different mutations of the CYLDI gene can give rise to distinct clinical and histological expression such as FC and MFT.

Freckles are numerous pigmented macules on the face commonly occurring in the Caucasian and Chinese population. As freckling is considered as an independent trait, no gene or locus for it has been identified to date. Here we performed genome-wide scan for linkage analysis in a multigeneration Chinese family with freckles. A maximum LOD score of 4.26 at a recombination fraction of 0 has been obtained with marker D4S1566. Haplotype analysis localized the freckles locus to a 16 Mbp region flanked by D4S2952 and D4S1607. We have thus mapped the gene for freckles to chromosome 4q32-q34. This will aid future identification of the responsible gene, which will be very useful for the understanding of the molecular mechanism of freckles.

Neurofibromatosis type 1 is a common neurocutaneous disorder, mostly caused by mutations in the NF1 gene. To identify the molecular genetic etiology of neurofibromatosis type 1 in two familiar and three sporadic cases of Han Chinese, DNA was isolated from the peripheral blood of eight patients in two NF1 pedigrees, three sporadic cases, and 100 unrelated healthy controls. Mutation screening for coding and exon-intron boundary sequences of NF1 gene was performed. Three novel missense mutations, c.601T>A in exon 4, c.871G>T in exon 6, and c.1448A>G in exon 10, were identified. These mutations provided new data for the spectrum of NF1 mutations causing neurofibromatosis type 1.

Vitiligo vulgaris is an acquired depigmenting disorder resulting from the loss of melanocytes in the skin. Though several putative susceptibility loci of vitiligo have been identified in different populations, the pathogenesis of the disease remains poorly understood. Through genetic linkage analysis of a large Chinese family cohort of vitiligo, we identified a vitiligo linkage locus AIS4 within chromosome 4q12-q21, a region containing several possible candidate genes, including the platelet-derived growth factor receptor alpha (PDGFRA) gene. We postulated that PDGFR mutations may be linked with vitiligo. To test this hypothesis, we performed DNA sequencing on this gene in 143 multiplex families with familial vitiligo vulgaris, 480 patients with sporadic vitiligo vulgaris, and 480 healthy subjects. Mutations were found in 3.5% of familial vitiligo cases, which is significantly higher than for the general population (0.42%, p = 0.008, Fisher's exact test), and possibly higher than in sporadic vitiligo patients (1.0%, p = 0.053). To our knowledge, this is the first observation that PDGFRA mutations are linked with familial vitiligo vulgaris.

Background Linkage studies suggest a locus, SLEB2, involved in susceptibility to systemic lupus erythematosus (SLE) and programmed cell death 1 (PDCD1) gene locates in this region. The association of PDCD1 polymorphism (PD1.3A/G) with SLE has been widely investigated, but there are no unambiguous conclusions. Objective To assess the combined evidence for the association between PD1.3A/G polymorphism and SLE and to summarize the effect size of the polymorphism associated with susceptibility to SLE. Methods We surveyed studies on the PD1.3A/G polymorphism and SLE using comprehensive PubMed search up to May 2008. The pooled odds ratio (OR) was calculated using a fixed- or a random-effects model. Heterogeneity was identified by sensitivity analysis and publication bias was examined by funnel plot and Egger's test. We also computed the power for a given number of samples. Results A total of 20 datasets from eight studies that met our inclusion criteria were included. The studies comprised of a total of 2909 cases and 3995 controls. Stratified meta-analysis demonstrated a significant association between PD1.3A and SLE among non-Spanish European descents [OR, 1.290; 95% confidence interval (95% CI), 1.098–1.516; z = 3.10, P = 0.002], while PD1.3G is the risk allele in Spanish populations (OR = 1.414, 95% CI = 1.075–1.862; z = 2.48, P = 0.013). Both results have sufficient power to support these findings. No publication bias presented in the studies analysed. Conclusions This meta-analysis demonstrates a significant association between PD1.3A and SLE among non-Spanish European descents, while a negative association was observed in Spanish population. Conflicts of interest None declared

PSORS1 (psoriasis susceptibility gene 1) is a major susceptibility locus for psoriasis. Several fine-mapping studies have highlighted a 300-kb candidate region of PSORS1 where multiple biologically plausible candidate genes were suggested. The most recent study has indicated HLA-Cw6 as the primary PSORS1 risk allele within the candidate region in a Caucasian population. In this study, a family-based association analysis of the PSORS1 locus was performed by analyzing 10 polymorphic microsatellite markers from the PSORS1 region as well as HLA-B, HLA-C and CDSN loci in 163 Chinese families of psoriasis. Five marker loci show strong evidence (P, Author Summary Psoriasis is a common skin disease with strong genetic risk. The analysis of psoriatic families with multiple affected individuals has identified several genomic regions that are linked (showing linkage evidence) to the development of psoriasis. Of them, the region on 6p21.3 (PSORS1) is a well-confirmed major risk locus. The identification of the disease risk gene within the PSOR1 locus, however, has been difficult, largely due to the fact that several genes show evidence for association with the disease development and the evidences are highly correlated and hard to be separated from each other. In this study, we performed a fine mapping study of the PSORS1 locus in Chinese families with psoriasis. By analyzing recombinant haplotypes that carry different risk-associated genetic variants within different genes, we were able to separate the genetic effects observed within multiple genes and identify strong supporting evidence for HLA-C to be the primary risk gene of the PSORS1 locus. We have further demonstrated that the genetic variation within the HLA-C gene does not explain the full linkage evidence at the PSORS1 locus, suggesting that there might be other risk genes and/or alleles within the region. Our findings have improved our understanding about the genetic complexity of the PSORS1 locus.

Background Pachyonychia congenita is an autosomal dominant disorder that usually develops in early infancy. The major features of the syndrome are hypertrophic nail dystrophy, palmoplantar keratoderma and oral leucokeratosis, accompanied by other ectodermal defects, according to subtype. Objective To analyse the K6a gene mutation in a sporadic Chinese patient with pachyonychia congenita type 1 (PC-1) and to explore the relationship between the genotype and phenotype of PC-1. Methods Genomic DNA was extracted from peripheral blood of the patient with PC-1 and 100 unrelated controls. The whole coding region of K6a gene was amplified using long-range polymerase chain reaction (PCR); nested PCR was then used to amplify the mutation ‘hot-spot’ of the K6a gene. The PCR products were directly sequenced to detect the mutation. Results A novel missense mutation L468Q in the helix 2B domain of the K6a polypeptide was identified in the patient but not in the healthy individuals from the family and 100 unrelated control individuals. Conclusions We describe this mutation for the first time, and provide further evidence that the helix boundary motif sequences of K6a are a mutation ‘hot-spot’.

Psoriasis is a heterogeneous disease for which nine linkage loci (PSORS loci 1-5 and PSORS7-10) have been accepted by the Human Genome Nomenclature Committee and an additional 16 potential susceptibility loci have been reported so far. Our previous genome-wide scan in 61 Chinese Han psoriasis vulgaris families found two susceptibility loci at 6p21.3 and 4q31 and additional suggestive linkage evidence at other regions, including 9q33. In this follow-up study, the linkage evidence at 9q33 was further investigated using an expanded sample of 160 families and improved marker coverage. Our follow-up linkage analysis of the 160 families demonstrated strong linkage evidence (Por = 0.000022) throughout a region between 133.38 and 146.23 cM with a maximum nonparametric linkage (NPL) score of 4.64 (P = 0.00000023) and a heterogeneity LOD (HLOD) score of 5.03 (alpha = 46%) at 142.39 cM near the marker D9S290. By stratifying the 160 families into the subtypes of 130 early-onset and 30 late-onset families, we revealed stronger linkage evidence in the early-onset psoriasis families with a maximum multipoint HLOD score of 6.48 (alpha = 58%) and a maximum NPL score of 4.69 (P = 0.00000012) near marker D9S290. Our follow-up study has confirmed a novel susceptibility locus at 9q33-34 for early-onset psoriasis in the Chinese population.

Summary Background. Acrokeratosis verruciformis of Hopf (AKV) is a rare genodermatosis characterized by multiple flat-topped, flesh-coloured papules on the dorsa of hands and feet, and punctuate keratoses on the palms and soles. A mutation in the ATP2A2 gene has been shown to be associated with AKV and with Darier's disease (DD). Objectives. To explore the molecular aetiology of AKV and DD. Methods. We investigated the clinical and histological information in two families and a sporadic case with AKV and one family and a sporadic case with DD in China. Mutation analysis of ATP2A2 was performed by PCR and direct sequencing, and genotyping and linkage analysis performed using six polymorphic microsatellite markers spanning the locus at 12q23–12q24 containing ATP2A2. Results. Mutational analysis showed no mutation in ATP2A2 among the AKV patients, but we found two novel mutations (p.C318F and p.M719fs) in the DD patients. The genotyping and linkage analysis results revealed no linkage evidence of the locus at 12q23–12q24 in a large AKV family. Conclusions. Our findings provide evidence for the genetic heterogeneity of AKV and demonstrate that mutations in genes other than ATP2A2 are responsible for AKV in a proportion of the Chinese population.

Acne inversa (hidradenitis suppurativa) is a chronic relapsing inflammatory skin disease characterized by recurrent draining sinuses and abscesses, predominantly in skin folds that carry terminal hairs and apocrine glands. The genetic basis for this disease is unknown. In this study, we performed a genome-wide scan in a four-generation Chinese family to map the chromosome location of the responsible gene. We first identified a locus at chromosome 1p21.1-1q25.3 with the maximum logarithm of odds (LOD) score of 3.26 at the marker D1S2624 (at recombination fraction=0.00). The other two-point LOD scores >/=3 were observed at markers D1S2695, D1S2726, D1S252, and D1S2777. Haplotype analysis localized this locus to a 76 Mb region flanked by D1S248 and D1S2711. This is the first locus for the inversa acne and will be a starting point towards understanding the molecular mechanisms of this disease.

Darier's disease (DD) is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. To date, at least 140 mutations in the ATP2A2 gene have been identified as the genetic basis of DD. Here we reported three familial and two sporadic Chinese DD patients totally with four missense mutations (N767D, M494I, M494L, C318F) and one splice-site mutation (1288-6A--G) in ATP2A2 gene, and presented a literature review of DD cases reported in China since 1989. Our data add new variants to the repertoire of ATP2A2 gene in DD and confirms that most mutations in the ATP2A2 gene are private and missense type. Likewise, the literature review indicates that DD is not uncommon in China and presents more information about genotype-phenotype correlations.