A novel mutation in SEPN1 causing rigid spine muscular dystrophy 1: A Case report

Abstract Background Muscular dystrophies are a clinically and genetically heterogeneous group of disorders characterized by variable degrees of progressive muscle degeneration and weakness. There is a wide variability in the age of onset, symptoms and rate of progression in subtypes of these disorders. Herein, we present the results of our study conducted to identify the pathogenic genetic variation involved in our patient affected by rigid spine muscular dystrophy. Case presentation A 14-year-old boy, product of a first-cousin marriage, was enrolled in our study with failure to thrive, fatigue, muscular dystrophy, generalized muscular atrophy, kyphoscoliosis, and flexion contracture of the knees and elbows. Whole-exome sequencing (WES) was carried out on the DNA of the patient to investigate all coding regions and uncovered a novel, homozygous missense mutation in SEPN1 gene (c. 1379 C > T, p.Ser460Phe). This mutation has not been reported before in different public variant databases and also our database (BayanGene), so it is classified as a variation of unknown significance (VUS). Subsequently, it was confirmed that the novel variation was homozygous in our patient and heterozygous in his parents. Different bioinformatics tools showed the damaging effects of the variant on protein. Multiple sequence alignment using BLASTP on ExPASy and WebLogo, revealed the conservation of the mutated residue. Conclusion We reported a novel homozygous mutation in SEPN1 gene that expands our understanding of rigid spine muscular dystrophy. Although bioinformatics analyses of results were in favor of the pathogenicity of the mutation, functional studies are needed to establish the pathogenicity of the variant

Modulations of cell cycle checkpoints during HCV associated disease

Background Impaired proliferation of hepatocytes has been reported in chronic Hepatitis C virus infection. Considering the fundamental role played by cell cycle proteins in controlling cell proliferation, altered regulation of these proteins could significantly contribute to HCV disease progression and subsequent hepatocellular carcinoma (HCC). This study aimed to identify the alterations in cell cycle genes expression with respect to early and advanced disease of chronic HCV infection. Methods Using freshly frozen liver biopsies, mRNA levels of 84 cell cycle genes in pooled RNA samples from patients with early or advanced fibrosis of chronic HCV infection were studied. To associate mRNA levels with respective protein levels, four genes (p27, p15, KNTC1 and MAD2L1) with significant changes in mRNA levels (\u3e 2-fold, p-value \u3c 0.05) were selected, and their protein expressions were examined in the liver biopsies of 38 chronic hepatitis C patients. Results In the early fibrosis group, increased mRNA levels of cell proliferation genes as well as cell cycle inhibitor genes were observed. In the advanced fibrosis group, DNA damage response genes were up-regulated while those associated with chromosomal stability were down-regulated. Increased expression of CDK inhibitor protein p27 was consistent with its mRNA level detected in early group while the same was found to be negatively associated with liver fibrosis. CDK inhibitor protein p15 was highly expressed in both early and advanced group, but showed no correlation with fibrosis. Among the mitotic checkpoint regulators, expression of KNTC1 was significantly reduced in advanced group while MAD2L1 showed a non-significant decrease. Conclusion Collectively these results are suggestive of a disrupted cell cycle regulation in HCV-infected liver. The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development

Towards a System Level Understanding of Non-Model Organisms Sampled from the Environment: A Network Biology Approach

The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations

مروري گذرا بر آرا و نظرات ابن سینا، اخوینی و تفلیسی در باب تب و تشخیص بیماری‌ها و مقایسه آن با طب نوین

Background: Since olden times, fever and its diagnostic features have been always paid attention to. The aim of this study was to investigate the views of Iranian Islamic scholars, Avicenna, Tbilisi and Akhaveayne on fever and their compatibility with modern sciences. Methods: The authors tried to refer to authentic and reliable sources for fever in traditional medicine and compare them with modern medicine and arrange their findings into a descriptive article. To collect valid data a comprehensive library search as well as an electronic one, using appropriate keywords, were carried out. Results: Based on the data collected and according to Iranian traditional medicine the root of fever lay in the disorders of other organs which could be helpful in the diagnosis of illnesses. In traditional medicine, fever was divided into different types like sanguine (of blood), melancholic, phlegmatic, daily fever, and so on.In Iranian traditional medicine careful examination of the patient as well as the background leading to fever were of utmost importance and a lot of foods prescribed for the treatment of fever were consistent with the standards of modern medicine. Conclusion: Given that in modern medicine many causes of fever are still unknown, a new approach to the traditional diagnostic and therapeutic views on fever can compensate for the insufficiencies of modern medicine in this regard.سابقه و هدف: توجه به تب و ویژگی‌های آن از گذشته نیز در تشخیص بیماری‌ها مورد توجه بوده است. هدف از مطالعه حاضر بررسی نظرات اندیشمندان ایران اسلامی شامل ابن سینا، اخوینی و تفلیسی در زمینه پدیده تب و تطابق آن با علوم جدید می‌باشد. روش بررسی: در این مقاله سعی شده است از طریق دسترسی به منابع معتبر در قالب یک مقاله توصیفی نظرات اندیشمندان ایران اسلامی در زمینه تب و تشخیص بیماری‌ها مورد بررسی و با علم پزشکی امروز مقایسه گردد. جهت این کار با استفاده از کلید واژه‌های مناسب و جستجوی الکترونیکی و دستی در منابع معتبر اطلاعات گرداوری و به هدف محوری پژوهش پرداخته شده است. یافته‌ها: بر اساس بررسی متون انجام شده در نگاه مکتب طب سنتی ایران تب می‌تواند ریشه در اختلالات دیگر اعضای بدن داشته باشد که در تشخیص بیماری‌ها کمک کننده است. همچنین انواع تب در طب سنتی ایران عبارت بودند از تب سودایی، تب دموی، تب روزانه، تب خلطی و انواع دیگر بودند. همچنین طب سنتی به معاینه دقیق بیمار و هر آنچه مربوط به بروز قبل از تب بوده توجه خاص داشته و بسیاری از درمان‌های غذایی تجویزی با موازین پزشکی نوین همخوانی داشته است. نتیجه‌گیری: با توجه به اینکه در طب نوین بسیاری از موارد تب به صورت ناشناخته باقی مانده و در اقدامات تشخیصی جوابی حاصل نمی‌گردد توجهی جدید به دیدگاه تشخیصی و درمانی اطبا سنتی می‌تواند بخشی از نارسایی طب نوین را ترمیم و قابلیت پاسخگویی آن را ارتقا داد.&nbsp