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Genome wide association studies (GWASs) have revealed multiple genetic variants associated with leprosy in the Chinese population. The aim of our study was to utilize the genetic variants to construct a risk prediction model through a weighted genetic risk score (GRS) in a Chinese set and to further assess the performance of the model in identifying higher-risk contact individuals in an independent set. The highest prediction accuracy, with an area under the curve (AUC) of 0.743 (95% confidence interval (CI): 0.729–0.757), was achieved with a GRS encompassing 25 GWAS variants in a discovery set that included 2,144 people affected by leprosy and 2,671 controls. Individuals in the high-risk group, based on genetic factors (GRS > 28.06), have a 24.65 higher odds ratio (OR) for developing leprosy relative to those in the low-risk group (GRS≤18.17). The model was then applied to a validation set consisting of 1,385 people affected by leprosy and 7,541 individuals in contact with leprosy, which yielded a discriminatory ability with an AUC of 0.707 (95% CI: 0.691–0.723). When a GRS cut-off value of 22.38 was selected with the optimal sensitivity and specificity, it was found that 39.31% of high risk contact individuals should be screened in order to detect leprosy in 64.9% of those people affected by leprosy. In summary, we developed and validated a risk model for the prediction of leprosy that showed good discrimination capabilities, which may help physicians in the identification of patients coming into contact with leprosy and are at a higher-risk of developing this condition. [ABSTRACT FROM AUTHOR]

Porokeratosis (PK) is a group of epidermal keratinization disorder exhibiting an autosomal dominant mode of inheritance, including five clinical subtypes: disseminated superficial actinic porokeratosis (DSAP), disseminated superficial porokeratosis (DSP), classic porokeratosis of Mibille (PM), porokeratosis palmaris et plantaris disseminate (PPPD) and linear porokeratosis (LP).To date, seven genes, MVK, MVD, FDPS, PMVK, SSH1, SART3 and SLC17A9 in six genetic loci, have been reported to be involved in the PK development, accounting for about 70% of patients [[1]]. Besides, three of the LP patients carried one PMVK mutation and two MVD mutations respectively, which is consistent with previous reports [[2], [5]]. [Extracted from the article]

The article focuses on a study which examines novel mutations of tuberous sclerosis complex 1 (TSC1) gene in Chinese patients with TSC. The researchers identified one SNP and one missense polymorphism in the study participants. Study results are considers useful in genetic counseling and in prenatal diagnosis of affected families.

Epidermolysis bullosa simplex, characterized by mechanical fragility and blistering within the basal layer of the epidermis, is a rare inherited skin disorder with a prevalence of about 1 in 25 000-50 000.[1] Mutations in several genes, including I KRT5 i , I KRT14 i , I PLEC i , I DSP i , I JUP i , I EXPH5, TGM5 i and I DST i , have been reported.[2] Among them, the mutations in I KRT5 i and I KRT14 i account for 75% of cases.[3] To date, a total of 143 and 112 I KRT5 i and I KRT14 i mutations have been reported, respectively (http://www.interfil.org). The basis for the disease likely involves protein-protein interactions between the two genes and their associated expression.[8] To date, five patients with digenic inheritance of epidermolysis bullosa simplex with I KRT5 i and I KRT14 i mutations have been reported. Among them, the probands' phenotypes in two families were more severe when compared to their affected parents carrying one single mutation in I KRT5 i or I KRT14 i .[[4]] The phenotypes and genetic mutations of reported cases are summarized in Table. [Extracted from the article]

Background Generalized pustular psoriasis (GPP) is a rare type of psoriasis with potentially life-threatening implications. Mutations in IL36RN gene have been suggested to be causative or predisposing factors for GPP. Objective To evaluate the genetic heterogeneity of GPP, PV and GPP alone, GPP with PV. Methods We performed a sanger sequencing identify IL36RN mutations in 62 Chinese Han patients with sporadic GPP, including 17 GPP without psoriasis vulgaris (PV) (GPP alone) cases vs. 45 GPP with preceding, later or accompanied by PV (GPP with PV) cases; 16 patients with pediatric-onset GPP (PGPP) vs. 46 adult-onset GPP (AGPP). We included 96 healthy controls and 174 sporadic patients with PV. Resuts We found 2 new variants and 4 known IL36RN variants in 29 GPP patients, 18 individuals carried recessive (homozygous/compound heterozygous) alleles and 11 cases harbored a single heterozygous change. Twelve PV patients and six controls harbored a single heterozygous for three out of the six variants. Significant differences were observed between GPP and PV groups, GPP alone and GPP with PV groups when compared frequencies of IL36RN variants, but we did not found association between PGPP and AGPP groups. Conclusion Our study provided more evidence that GPP and PV are distinct subtypes of psoriasis caused by different pathogenesis, and GPP alone could be regarded as an especial entities of GPP which is different from GPP with PV on the etiology. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 46-year-old Chinese woman who suffers from slightly painful and pale blue nodes on her forearm for 30 years, on her face and scalp for 10 years and her 25-year-old nephew has similar lesion on the face. The patients were diagnosed with Brooke-Spiegler syndrome (BSS) and trichoepithelioma, respectively. Mutations in the CYLD gene were considered as the cause of the syndrome.

The article presents a study on the mutations of the ATP2A2 gene in Chinese patients with Darier disease. Topics discussed include information on the Darier disease as a rare autosomal dominant genodermatosis with almost complete penetrance, characterized by abnormal keratinization and acantholysis; discussions on the clinical manifestations include multiple dark-brown keratotic plaques and warty papules covered by thick crusts particularly in seborrheic areas.

The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4456 psoriasis cases and 6027 controls of Chinese population using the Mass ARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 ( P=6.15×10−5, OR=5.07), rs16861329 on 3q27.3 ( P=2.02×10−4, OR=0.87) and rs849135 on 7p15.1 ( P=6.59×10−9, OR=1.78), which suggested PTPN22, ST6 GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. Our findings implicated the involvement of T-cell receptor signalling pathway in the pathogenesis of psoriasis and further confirmed the shared genetic susceptibility between psoriasis and diabetes. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have led to the discovery of several susceptibility loci for leprosy with robust evidence, providing biological insight into the role of host genetic factors in mycobacterial infection. However, the identified loci only partially explain disease heritability, and additional genetic risk factors remain to be discovered. We performed a 3-stage GWAS of leprosy in the Chinese population using 8,313 cases and 16,017 controls. Besides confirming all previously published loci, we discovered six new susceptibility loci, and further gene prioritization analysis of these loci implicated BATF3, CCDC88B and CIITA-SOCS1 as new susceptibility genes for leprosy. A systematic evaluation of pleiotropic effects demonstrated a high tendency for leprosy susceptibility loci to show association with autoimmunity and inflammatory diseases. Further analysis suggests that molecular sensing of infection might have a similar pathogenic role across these diseases, whereas immune responses have discordant roles in infectious and inflammatory diseases. [ABSTRACT FROM AUTHOR]

This article discusses two cases of fever, rash, and organ involvement during the treatment of leprosy. The first patient, a 65-year-old man, developed a high fever and a generalized rash after 27 days of treatment. The second patient, a 39-year-old woman, developed a fever and a pruritic rash 21 days after treatment. The symptoms in both cases were initially suspected to be a drug-induced hypersensitivity syndrome (DIHS) caused by the medication dapsone (DDS). The diagnosis of DDS-induced hypersensitivity syndrome was confirmed through an HLA-B*13:01 test. Treatment with corticosteroids led to improvement in both patients. The article emphasizes the importance of timely diagnosis and differential diagnosis in the treatment of leprosy and highlights the value of the HLA-B*13:01 test in preventing DDS syndrome. [Extracted from the article]

The article presents two case studies of fever, rush, and organ involvement during leprosy therapy. The first case involves a 65-year-old man who was diagnosed with borderline tuberculoid leprosy, while the other patient is a 39-year-old woman who was diagnosed with lepromatous leprosy. Both patients were given a final diagnosis of dapsone induced hypersensitivity syndrome, described as a life threatening condition in treating leprosy. A discussion about DDS Syndrome is also provided.

Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmented anomaly mainly affecting flexures. Though KRT5 has been identified to be the causal gene of DDD, the heterogeneity of this disease was displayed: for example, POFUT1 and POGLUT1 were recently identified and confirmed to be additional pathogenic genes of DDD. To identify other DDD causative genes, we performed genome-wide linkage and exome sequencing analyses in a multiplex Chinese DDD family, in which the KRT5 mutation was absent. Only a novel 1-bp deletion (c.246+5delG) in POFUT1 was found. No other novel mutation or this deletion was detected in POFUT1 in a second DDD family and a sporadic DDD case by Sanger Sequencing. The result shows the genetic-heterogeneity and complexity of DDD and will contribute to the further understanding of DDD genotype/phenotype correlations and to the pathogenesis of this disease. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease that is primarily characterized by multiple café au-lait spots (CALs) and skin neurofibromas, which are attributed to defects in the tumor suppressor NF1. Because of the age-dependent presentation of NF1, it is often difficult to make an early clinical diagnosis. Moreover, identifying genetic alterations in NF1 patients represents a complex challenge. Currently, there are no effective detective methods, and no comprehensive NF1 mutation data are available for mainland China. We screened 109 Chinese patients from 100 families with NF1-like phenotypes (e.g., CALs, neurofibromas, etc.) using Sanger sequencing, multiplex ligation-dependent probe amplification and cDNA sequencing. NF1 mutations were identified in 97 individuals, among which 34 intragenic mutations have not previously been reported. Our exhaustive mutational analysis detected mutations in 89% (89/100) of the NF1-like probands and 93% (70/75) of subjects fulfilling the National Institutes of Health (NIH) criteria. Our findings indicate that individuals who exclusively present with multiple CALs exhibit a high possibility (76%) of having NF1 and show a significantly lower mutation rate (p = 0.042) compared with subjects who fulfill the NIH criteria, providing clinicians with the information that subjects only with multiple CALs harbor a considerable possibility (24%) of being attributed to other comparable diseases. [ABSTRACT FROM AUTHOR]

Background: As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH) had remained unclear until recently when ABCB6 was reported as a causative gene of DUH. Methodology: We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation. Results: Genome-wide linkage (assuming autosomal dominant inheritance mode) and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val) that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val) and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys) in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them. Conclusion: Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma. [ABSTRACT FROM AUTHOR]

Of eight leprosy susceptibility loci identified by genome-wide association studies, five have been implicated in Crohn disease, suggesting a common genetic fingerprint between leprosy and inflammatory bowel disease (IBD). Here, we conducted a multiple-stage genetic association study of 133 IBD susceptibility loci in multiple leprosy samples (totaling 4,971 leprosy cases and 5,503 controls) from a Chinese population and discovered two associations at rs2058660 on 2q12.1 (p = 4.57 × 10−19; odds ratio [OR] = 1.30) and rs6871626 on 5q33.3 (p = 3.95 × 10−18; OR = 0.75), implicating IL18RAP/IL18R1 and IL12B as susceptibility genes for leprosy. Our study reveals the important role of IL12/IL18-mediated transcriptional regulation of IFN-γ production in leprosy, and together with previous findings, it demonstrates the shared genetic susceptibility between infectious and inflammatory diseases. [Copyright &y& Elsevier]

We performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance: rs2275606 (combined P = 3.94 × 10?14, OR = 1.30) on 6q24.3 and rs3762318 (combined P = 3.27 × 10?11, OR = 0.69) on 1p31.3. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy. Furthermore, we identified evidence of interaction between the NOD2 and RIPK2 loci, which is consistent with the biological association of the proteins encoded by these genes (NOD2-RIPK2 complex) in activating the NF-?B pathway as a part of the host defense response to infection. Our findings have expanded the biological functions of IL23R by uncovering its involvement in infectious disease susceptibility and suggest a potential involvement of autophagocytosis in leprosy pathogenesis. The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the analysis of caspase recruitment domain family member 14 (CARD14) variants in the Chinese Han patients with psoriasis vulgaris (PsV) and generalized pustular psoriasis (GPP). Findings reveal five rare variants including p.Met119Val, p.Arg166His, and p.Ala216Thr. It suggests the significant role of the rare CARD14 variants in the pathogenesis of GPP.

Background: Herpes simplex virus type-2 (HSV-2) infection is the main cause of genital ulcer disease and increases the risk of HIV acquisition. Little information is available regards the epidemiological characteristics of HSV-2 among general population in China. The aim of this study was to explore seroprevalence and associated factors of HSV-2 and provide information for design of HSV-2 control strategy in Shandong, China.Methods: In this cross-sectional study, a total of 8074 persons, 18-49 years of age, were selected using multi-stage probability sampling to represent the general population of Shandong in 2016. Demographic data were collected through face-to-face interviews. Other variables were obtained by self-administered questionnaire surveys. Blood was collected for HSV-2 IgG detection with ELISA.Results: A total of 7256 sexually-active participants were included in the analysis. The weighted seroprevalence of HSV-2 infection was 4.2% (95% confidence interval [CI], 3.2-5.3) in females, which was significant higher than that in males (2.7%; 95% CI, 1.1-4.2) (P = 0.04). The seroprevalence of HSV-2 was higher in individuals from eastern region (6.4%; 95% CI, 5.9-6.9) and urban areas (4.3%; 95% CI, 2.6-6.0) of Shandong than those from other regions (P < 0.01). Associated factors for HSV-2 infection among men were being urban residents (adjusted odds ratio [AOR], 2.36; 95% CI, 1.14-4.88), having two or more sex partners in the past year (AOR, 3.22; 95% CI, 1.90-5.43) and having commercial sex (AOR, 1.51; 95% CI, 1.00-2.26). Among females, being divorced or widowed (AOR, 1.79; 95% CI, 1.08-2.97), having a tattoo (AOR, 2.89; 95% CI, 1.07-7.84), and being dissatisfied with the sex activity quality (AOR, 2.12; 95% CI, 1.24-3.63) was associated with HSV-2 infection.Conclusions: This study showed a relatively low burden of HSV-2 in Shandong province, China compared with the seroprevalence reported in many other provinces and countries. HSV-2 control programs in Shandong should focus on eastern, urban and female residents, and pay more attention to individuals with identified associated factors. [ABSTRACT FROM AUTHOR]

Background: A population-based study of Chlamydia trachomatis (CT) infections is essential in designing a specific control program; however, no large investigation of CT infections among the general population in mainland China has been conducted since 2000. We aimed to determine the prevalence, risk factors, and associated medical costs of CT among residents, 18-49 years of age, in Shandong, China.Methods: From May to August 2016, a multistage probability sampling survey involving 8074 individuals was distributed. Data were collected via face-to-face interviews, followed by self-administered questionnaire surveys. First-void urines were collected and tested for CT and Neisseria gonorrhoeae (NG) using nucleic acid amplification.Results: The weighted prevalence of CT infection was 2.3% (95% confidence interval [CI], 1.5-3.2) in females and 2.7% (1.6-3.8) in males. Women, 30-34 years of age, had the highest prevalence of CT infections (3.5%, 2.6-4.4), while the highest prevalence of CT infections in males was in those 18-24 years of age (4.3%, 0.0-8.8). Neisseria gonorrhoeae infection had a prevalence of 0.1% (0.0-0.3) in women and 0.03% (0.0-0.1) in men. Risk factors for CT infections among females included being unmarried, divorced, or widowed (odds ratio [OR], 95% CI 3.57, 1.54-8.24) and having two or more lifetime sex partners (3.72, 1.14-12.16). Among males, first intercourse before 20 years of age (1.83, 1.10-3.02) and having two or more lifetime sex partners (1.85, 1.14-3.02) were associated with CT infections. The estimated lifetime cost of CT infections in patients 18-49 years of age in Shandong was 273 million (range, 172-374 million) China Renminbi in 2016.Conclusions: This study demonstrated a high burden of CT infections among females < 35 years of age and males < 25 years of age in Shandong. Thus, a CT infection control program should focus on this population, as well as others with identified risk factors. [ABSTRACT FROM AUTHOR]

Summary Objective Leprosy and tuberculosis (TB) are chronic granulomatous infectious diseases. As well as pathogen and environmental factors, host genetic factors make a substantial contribution to susceptibility to both diseases. More importantly, leprosy and TB also have pathogenic mechanisms and clinical features in common. In this study, the genetic association between leprosy and TB was investigated in a Chinese Han population. Methods A genetic association study that included 46 TB susceptibility single nucleotide polymorphisms (SNPs) was performed, involving 1150 leprosy cases and 1150 controls from the Chinese Han population. The Sequenom MassARRAY system was used. Results No significant association was found between the 46 SNPs and leprosy. Therefore, according to the present study, there is no shared susceptibility locus between leprosy and TB in the Chinese Han population. Conclusions Although leprosy and TB have a number of similar characteristics, no shared susceptibility loci were found in the Chinese Han population. Thus, this study demonstrated that the genetic basis of the pathogenesis of the two diseases may vary greatly. [ABSTRACT FROM AUTHOR]

The article focuses on the Genome-Wide Association Study of single nucleotide polymorphisms (SNP) of association of PARK2 and PACRG with leprosy in Chinese population. The study found no remarkable association of Chinese population with the risk SNPs within the PARK2 and PACRG leprosy region. It is noted that there may be a suggestive association of SNPs with ethnic heterogeneity of susceptibility to leprosy.