Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (∼12.5%, P = 0.036), particularly in drug-naïve patients (∼20%, P = 0.011), and a trend toward hypermethylation in their first-degree relatives (P = 0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (∼80%, P = 0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance.

Epidermolysis bullosa (EB), the paradigm of heritable skin fragility disorders, is associated with mutations in as many as 20 distinct genes. One of the clinical variants, recessive dystrophic EB (RDEB), demonstrates sub-lamina densa blistering accompanied by alterations in anchoring fibrils due to mutations in COL7A1. In this study, we characterized a patient with widespread connective tissue abnormalities, including skin blistering similar to that in RDEB. Whole exome sequencing, combined with genome-wide homozygosity mapping, identified a homozygous missense mutation in PLOD3 encoding lysyl hydroxylase 3 (LH3). No mutations in COL7A1, the gene previously associated with RDEB, were detected. The level of LH3 was dramatically reduced in the skin and fibroblast cultures from the patient. The blistering in the skin occurred below the lamina densa and was associated with variable density and morphology of anchoring fibrils. The level of type VII collagen expression in the skin was markedly reduced. Analysis of hydroxylysine and its glycosylated derivatives (galactosyl-hydroxylysine and glucosyl-galactosyl-hydroxylysine) revealed marked reduction in glycosylated hydroxylysine. Collectively, these findings indicate that PLOD3 mutations can result in a dystrophic EB-like phenotype in the spectrum of connective tissue disorders and add it to the list of candidate genes associated with skin fragility.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition and the most common liver disease worldwide, affecting more than one-third of the population. So far there have been no reports on mendelian inheritance in families with NAFLD. Methods:We performed whole-exome or targeted next-generation sequencing on patients with autosomal dominant NAFLD. Results:We report a heritable form of NAFLD and/or dyslipidemia due to monoallelic ABHD5 mutations, with complete clinical expression after the fourth decade of life, in 7 unrelated multiplex families encompassing 39 affected individuals. The prevalence of ABHD5-associated NAFLD was estimated to be 1 in 1,137 individuals in a normal population. Conclusion:We associate a Mendelian form of NAFLD and/or dyslipidemia with monoallelic ABHD5 mutations.

Objectives: This study aimed to acquire knowledge about the factors affecting smartphone adoption for accessing information in medical settings in Iranian Hospitals. Methods: A qualitative and quantitative approach was used to conduct this study. Semi-structured interviews were conducted with 21 medical residents and interns in 2013 to identify determinant factors for smartphone adoption. Afterwards, nine relationships were hypothesised. We developed a questionnaire to test these hypotheses and to evaluate the importance of each factor. Structural equation modelling was used to analyse the causal relations between model parameters and to accurately identify determinant factors. Results: Eight factors were identified in the qualitative phase of the study, including perceived usefulness, perceived ease of use, training, internal environment, personal experience, social impacts, observability and job related characteristics. Among the studied factors, perceived usefulness, personal experience and job related characteristics were significantly associated with attitude to use a smartphone which accounted for 64% of the variance in attitude. Perceived usefulness had the strongest impact on attitude to use a smartphone. Conclusion: The factors that emerged from interviews were consistent with the Technology Acceptance Model (TAM) and some previous studies. TAM is a reliable model for understanding the factors of smartphone acceptance in medical settings.Keywords: consumer health information; information management; information seeking behaviour; social media Key messages• Perceived usefulness, personal experience and job related characteristics were the main factors predicting attitude to use a smartphone for accessing information in medical settings.• The Technology Acceptance Model (TAM) provides a good framework for understanding the factors behind the adoption of smartphones for accessing information in medical settings.• Librarians in medical settings and hospitals should provide health care professionals with highly used and licensed mobile medical resources.

BackgroundHyaline fibromatosis syndrome (HFS) is a rare heritable multi-systemic disorder with significant dermatologic manifestations. It is caused by mutations in ANTXR2, which encodes a transmembrane receptor involved in collagen VI regulation in the extracellular matrix. Over 40 mutations in the ANTXR2 gene have been associated with cases of HFS. Variable severity of the disorder in different patients has been proposed to be related to the specific mutations in these patients and their location within the gene.Case presentationIn this report, we describe four cases of HFS from consanguineous backgrounds. Genetic analysis identified a novel homozygous frameshift deletion c.969del (p.Ile323Metfs*14) in one case, the previously reported mutation c.134 T > C (p.Leu45Pro) in another case, and the recurrent homozygous frameshift mutation c.1073dup (p.Ala359Cysfs*13) in two cases. The epidemiology of this latter mutation is of particular interest, as it is a candidate for inhibition of nonsense-mediated mRNA decay. Haplotype analysis was performed to determine the origin of this mutation in this consanguineous cohort, which suggested that it may develop sporadically in different populations.ConclusionsThis information provides insights on genotype-phenotype correlations, identifies a previously unreported mutation in ANTXR2, and improves the understanding of a recurrent mutation in HFS.

The matriptase-prostasin cascade is a series of proteolytic reactions playing critical roles in multiple epithelial tissues. [1] Specifically, this cascade has unique components and functions in the epidermis. The matriptase-prostasin proteolytic cascade has been the subject of extensive recent dermatologic research, which has clarified its role in regulating differentiation and desquamation in the epidermis and follicular units. Additionally, genetic alterations in proteases in this cascade have been associated with human dermatologic diseases, including ichthyosis-hypotrichosis syndrome (IHS) and Netherton syndrome (NS). The matriptase-prostasin cascade is thus essential for proper epidermal function, and its dysfunction has clinical consequences. Given the relevance of this pathway to dermatology, we here provide an updated review of this cascade, with critical insight into multiple dermatologic diseases.

Viruses are one of the most important concerns for human health, and overcoming viral infections is a worldwide challenge. However, researchers have been trying to manipulate viral genomes to overcome various disorders, including cancer, for vaccine development purposes. CRISPR (clustered regularly interspaced short palindromic repeats) is becoming one of the most functional and widely used tools for RNA and DNA manipulation in multiple organisms. This approach has provided an unprecedented opportunity for creating simple, inexpensive, specific, targeted, accurate, and practical manipulations of viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus-1 (HIV-1), and vaccinia virus. Furthermore, this method can be used to make an effective and precise diagnosis of viral infections. Nevertheless, a valid and scientifically designed CRISPR system is critical to make more effective and accurate changes in viruses. In this review, we have focused on the best and the most effective ways to design sgRNA, gene knock-in(s), and gene knock-out(s) for virus-targeted manipulation. Furthermore, we have emphasized the application of CRISPR technology in virus diagnosis and in finding significant genes involved in virus-host interactions.

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