Hereditary Hearing Impairment with Cutaneous Abnormalities
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1 Evidence for Gliadin Antibodies As Causative Agents in Schizophrenia
1 Evidence for gliadin antibodies as causative agents in schizophrenia. C.J.Carter PolygenicPathways, 20 Upper Maze Hill, Saint-Leonard’s on Sea, East Sussex, TN37 0LG [email protected] Tel: 0044 (0)1424 422201 I have no fax Abstract Antibodies to gliadin, a component of gluten, have frequently been reported in schizophrenia patients, and in some cases remission has been noted following the instigation of a gluten free diet. Gliadin is a highly immunogenic protein, and B cell epitopes along its entire immunogenic length are homologous to the products of numerous proteins relevant to schizophrenia (p = 0.012 to 3e-25). These include members of the DISC1 interactome, of glutamate, dopamine and neuregulin signalling networks, and of pathways involved in plasticity, dendritic growth or myelination. Antibodies to gliadin are likely to cross react with these key proteins, as has already been observed with synapsin 1 and calreticulin. Gliadin may thus be a causative agent in schizophrenia, under certain genetic and immunological conditions, producing its effects via antibody mediated knockdown of multiple proteins relevant to the disease process. Because of such homology, an autoimmune response may be sustained by the human antigens that resemble gliadin itself, a scenario supported by many reports of immune activation both in the brain and in lymphocytes in schizophrenia. Gluten free diets and removal of such antibodies may be of therapeutic benefit in certain cases of schizophrenia. 2 Introduction A number of studies from China, Norway, and the USA have reported the presence of gliadin antibodies in schizophrenia 1-5. Gliadin is a component of gluten, intolerance to which is implicated in coeliac disease 6. -
Case Study: Testing for Genetic Disorders
Case study: Testing for genetic disorders Purpose: A genetic disorder is a disorder that is caused by an abnormality (or several abnormalities) in a person’s genome. Genetic disorders are often hereditary, which means they are passed down to a child from its parents. The most common genetic disorder is familial hypercholesterolaemia (a genetic predisposition to high cholesterol levels), which is thought to affect 1 in 250 people in the UK. Other disorders, such as cystic fibrosis, are rarer although they can be relatively common in particular ethnic groups; for instance, the incidence of cystic fibrosis in Scotland is almost double the global average. Collectively genetic disorders affect lots of people because there are more than 10,000 different types worldwide. Genetic testing is used to inform people whether they have a disorder, or if there is a chance they might pass a disorder on to their children. Photo credit: jxfzsy/ iStockphoto Photo credit: monkeybusiness/ iStockphoto Approaches to identifying genetic disorders In the UK, if a person is concerned they might have, or might develop, a genetic disorder based on their family history, they can: Go to their GP, who might refer them for genetic testing. Patients usually provide a DNA sample, which is then analysed for a specific abnormality. Usually a single gene will be tested, but whole-genome sequencing approaches are being developed. The 100,000 Genomes Project, for example, aims to study whole-genome sequences from patients with cancer and rare disease Use a commercial genetic testing service. In this case, customers collect samples of their own DNA and send them away for analysis and interpretation Take no action. -
Core Transcriptional Regulatory Circuitries in Cancer
Oncogene (2020) 39:6633–6646 https://doi.org/10.1038/s41388-020-01459-w REVIEW ARTICLE Core transcriptional regulatory circuitries in cancer 1 1,2,3 1 2 1,4,5 Ye Chen ● Liang Xu ● Ruby Yu-Tong Lin ● Markus Müschen ● H. Phillip Koeffler Received: 14 June 2020 / Revised: 30 August 2020 / Accepted: 4 September 2020 / Published online: 17 September 2020 © The Author(s) 2020. This article is published with open access Abstract Transcription factors (TFs) coordinate the on-and-off states of gene expression typically in a combinatorial fashion. Studies from embryonic stem cells and other cell types have revealed that a clique of self-regulated core TFs control cell identity and cell state. These core TFs form interconnected feed-forward transcriptional loops to establish and reinforce the cell-type- specific gene-expression program; the ensemble of core TFs and their regulatory loops constitutes core transcriptional regulatory circuitry (CRC). Here, we summarize recent progress in computational reconstitution and biologic exploration of CRCs across various human malignancies, and consolidate the strategy and methodology for CRC discovery. We also discuss the genetic basis and therapeutic vulnerability of CRC, and highlight new frontiers and future efforts for the study of CRC in cancer. Knowledge of CRC in cancer is fundamental to understanding cancer-specific transcriptional addiction, and should provide important insight to both pathobiology and therapeutics. 1234567890();,: 1234567890();,: Introduction genes. Till now, one critical goal in biology remains to understand the composition and hierarchy of transcriptional Transcriptional regulation is one of the fundamental mole- regulatory network in each specified cell type/lineage. -
Keratosis Follicularis Spinulosa Decalvans in a Female Child- a Rare Presentation Chowdhury J1, Ghoshal L2, Bannerjee S3
Bangladesh Journal of Medical Science Vol. 16 No. 04 October’17 Case report: Keratosis Follicularis Spinulosa Decalvans in a female child- a rare presentation Chowdhury J1, Ghoshal L2, Bannerjee S3 Abstract: Congenital alopecia universalis is a very rare presentation. A 6 year old girl came to us with total alopecia and multiple horny keratosis pilaris like skin lesions all over the body. The alopecia was mostly non-scarring with a few patches of scarring over the scalp. Histology from scalp revealed follicular plugging with perifollicular infiltrate of lymphocytes and plasma cells. The case was diagnosed as Keratosis follicularis spinulosa decalvans. This is very rare and even rarer in females. Keywords: keratosis pilaris; scarring alopecia; non-scarring alopecia Bangladesh Journal of Medical Science Vol. 16 No. 04 October’17. Page : 591-593 Introduction: Keratosis follicularis spinulosa Except a few brittle hairs on the crown area hair was decalvans is a rare genodermatosis that affects absent all over the scalp, eyelids and body. There predominantly males. It appears in infancy or were a few small patches of non-scarring alopecia childhood, and is characterized by diffuse follicular over the scalp [Figure 3]. keratotic papules associated with progressive Palms, soles, nail and mucosa were unaffected. cicatricial alopecia of the scalp, eyebrows and Family history was unremarkable with no history eyelashes. Family history is often positive. We report of consanguinity. Her twin sister was unaffected. a case of KFSD in a female child. There was no history of photophobia, no evidence Case-report: A 6 year old girl presented with of physical or mental retardation. -
DOI: 10.4274/Jcrpe.Galenos.2021.2020.0175
DOI: 10.4274/jcrpe.galenos.2021.2020.0175 Case report A novel SCNN1A variation in a patient with autosomal-recessive pseudohypoaldosteronism type 1 Mohammed Ayed Huneif1*, Ziyad Hamad AlHazmy2, Anas M. Shoomi 3, Mohammed A. AlGhofely 3, Dr Humariya Heena 5, Aziza M. Mushiba 4, Abdulhamid AlSaheel3 1Pediatric Endocrinologist at Najran university hospital, Najran Saudi Arabia. 2 Pediatric Endocrinologist at Al yamammah hospital, , Riyadh, Saudi Arabia. 3 Pediatric Endocrinologist at Pediatric endocrine department,. Obesity, Endocrine, and Metabolism Center, , King Fahad Medical City, Riyadh, Saudi Arabia. 4Clinical Geneticist, Pediatric Subspecialties Department, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia. 5 Research Center, King Fahad Medical City, Riyadh , Saudi Arabia What is already known on this topic ? Autosomal-recessive pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disorder caused by different variations in the ENaC subunit genes. Most of these variations appear in SCNN1A mainly in exon eight, which encodes for the alpha subunit of the epithelial sodium channel ENaC. Variations are nonsense, single-base deletions or insertions, or splice site variations, leading to mRNA and proteins of abnormal length. In addition, a few new missense variations have been reported. What this study adds ? We report a novel mutation [ c.729_730delAG (p.Val245Glyfs*65) ] in the exon 4 of the SCNN1A gene In case of autosomal recessive pseudohypoaldosteronism type 1. Patient with PHA1 requires early recognition, proper treatment, and close follow-up. Parents are advised to seek genetic counseling and plan future pregnancies. proof Abstract Pseudohypoaldosteronism type 1 (PHA1) is an autosomal-recessive disorder characterized by defective regulation of body sodium levels. -
EXTENDED CARRIER SCREENING Peace of Mind for Planned Pregnancies
Focusing on Personalised Medicine EXTENDED CARRIER SCREENING Peace of Mind for Planned Pregnancies Extended carrier screening is an important tool for prospective parents to help them determine their risk of having a child affected with a heritable disease. In many cases, parents aren’t aware they are carriers and have no family history due to the rarity of some diseases in the general population. What is covered by the screening? Genomics For Life offers a comprehensive Extended Carrier Screening test, providing prospective parents with the information they require when planning their pregnancy. Extended Carrier Screening has been shown to detect carriers who would not have been considered candidates for traditional risk- based screening. With a simple mouth swab collection, we are able to test for over 419 genes associated with inherited diseases, including Fragile X Syndrome, Cystic Fibrosis and Spinal Muscular Atrophy. The assay has been developed in conjunction with clinical molecular geneticists, and includes genes listed in the NIH Genetic Test Registry. For a list of genes and disorders covered, please see the reverse of this brochure. If your gene of interest is not covered on our Extended Carrier Screening panel, please contact our friendly team to assist you in finding a gene test panel that suits your needs. Why have Extended Carrier Screening? Extended Carrier Screening prior to pregnancy enables couples to learn about their reproductive risk and consider a complete range of reproductive options, including whether or not to become pregnant, whether to use advanced reproductive technologies, such as preimplantation genetic diagnosis, or to use donor gametes. -
Seq2pathway Vignette
seq2pathway Vignette Bin Wang, Xinan Holly Yang, Arjun Kinstlick May 19, 2021 Contents 1 Abstract 1 2 Package Installation 2 3 runseq2pathway 2 4 Two main functions 3 4.1 seq2gene . .3 4.1.1 seq2gene flowchart . .3 4.1.2 runseq2gene inputs/parameters . .5 4.1.3 runseq2gene outputs . .8 4.2 gene2pathway . 10 4.2.1 gene2pathway flowchart . 11 4.2.2 gene2pathway test inputs/parameters . 11 4.2.3 gene2pathway test outputs . 12 5 Examples 13 5.1 ChIP-seq data analysis . 13 5.1.1 Map ChIP-seq enriched peaks to genes using runseq2gene .................... 13 5.1.2 Discover enriched GO terms using gene2pathway_test with gene scores . 15 5.1.3 Discover enriched GO terms using Fisher's Exact test without gene scores . 17 5.1.4 Add description for genes . 20 5.2 RNA-seq data analysis . 20 6 R environment session 23 1 Abstract Seq2pathway is a novel computational tool to analyze functional gene-sets (including signaling pathways) using variable next-generation sequencing data[1]. Integral to this tool are the \seq2gene" and \gene2pathway" components in series that infer a quantitative pathway-level profile for each sample. The seq2gene function assigns phenotype-associated significance of genomic regions to gene-level scores, where the significance could be p-values of SNPs or point mutations, protein-binding affinity, or transcriptional expression level. The seq2gene function has the feasibility to assign non-exon regions to a range of neighboring genes besides the nearest one, thus facilitating the study of functional non-coding elements[2]. Then the gene2pathway summarizes gene-level measurements to pathway-level scores, comparing the quantity of significance for gene members within a pathway with those outside a pathway. -
Stelios Pavlidis3, Matthew Loza3, Fred Baribaud3, Anthony
Supplementary Data Th2 and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in UBIOPRED Chih-Hsi Scott Kuo1.2, Stelios Pavlidis3, Matthew Loza3, Fred Baribaud3, Anthony Rowe3, Iaonnis Pandis2, Ana Sousa4, Julie Corfield5, Ratko Djukanovic6, Rene 7 7 8 2 1† Lutter , Peter J. Sterk , Charles Auffray , Yike Guo , Ian M. Adcock & Kian Fan 1†* # Chung on behalf of the U-BIOPRED consortium project team 1Airways Disease, National Heart & Lung Institute, Imperial College London, & Biomedical Research Unit, Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom; 2Department of Computing & Data Science Institute, Imperial College London, United Kingdom; 3Janssen Research and Development, High Wycombe, Buckinghamshire, United Kingdom; 4Respiratory Therapeutic Unit, GSK, Stockley Park, United Kingdom; 5AstraZeneca R&D Molndal, Sweden and Areteva R&D, Nottingham, United Kingdom; 6Faculty of Medicine, Southampton University, Southampton, United Kingdom; 7Faculty of Medicine, University of Amsterdam, Amsterdam, Netherlands; 8European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, France. †Contributed equally #Consortium project team members are listed under Supplementary 1 Materials *To whom correspondence should be addressed: [email protected] 2 List of the U-BIOPRED Consortium project team members Uruj Hoda & Christos Rossios, Airways Disease, National Heart & Lung Institute, Imperial College London, UK & Biomedical Research Unit, Biomedical Research Unit, Royal -
Rozex Cream Ds
New Zealand Datasheet 1 PRODUCT NAME ROZEX® CREAM 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Metronidazole 7.5 mg/g 3 PHARMACEUTICAL FORM Contains 0.75% w/w metronidazole as the active ingredient in an oil-in-water cream base containing 4 CLINICAL PARTICULARS 4.1 Therapeutic indications ROZEX CREAM is indicated for the treatment inflammatory papules and pustules of rosacea. 4.2 Dosage and method of administration ROZEX CREAM should be applied in a thin layer to the affected areas of the skin twice daily, morning and evening. Areas to be treated should be washed with a mild cleanser before application. Patients may use non-comedogenic and non-astringent cosmetics after application of ROZEX CREAM. The dosage does not need to be adjusted for elderly patients. Safety and effectiveness in paediatric patients have not been established. ROZEX is not recommended for use in children. The average period of treatment is three to four months. The recommended duration of treatment should not be exceeded. If a clear benefit has been demonstrated continued therapy for a further three to four months period may be considered by the prescribing physician depending upon the severity of the condition. Clinical experience with ROZEX CREAM over prolonged periods is limited at present. Patients should be monitored to ensure that clinical benefit continues and that no local or systemic events occur. In the absence of a clear clinical improvement therapy should be stopped. ROZEX CREAM should not be used in or close to the eyes. The use of a sunscreen is recommended when exposure to sunlight cannot be avoided. -
A Network of Bhlhzip Transcription Factors in Melanoma: Interactions of MITF, TFEB and TFE3
A network of bHLHZip transcription factors in melanoma: Interactions of MITF, TFEB and TFE3 Josué A. Ballesteros Álvarez Thesis for the degree of Philosophiae Doctor January 2019 Net bHLHZip umritunarþátta í sortuæxlum: Samstarf milli MITF, TFEB og TFE3 Josué A. Ballesteros Álvarez Ritgerð til doktorsgráðu Leiðbeinandi/leiðbeinendur: Eiríkur Steingrímsson Doktorsnefnd: Margrét H. Ögmundsdóttir Þórarinn Guðjónsson Jórunn E. Eyfjörð Lars Rönnstrand Janúar 2019 Thesis for a doctoral degree at tHe University of Iceland. All rigHts reserved. No Part of tHis Publication may be reProduced in any form witHout tHe Prior permission of the copyright holder. © Josue A. Ballesteros Álvarez. 2019 ISBN 978-9935-9421-4-2 Printing by HáskólaPrent Reykjavik, Iceland 2019 Ágrip StjórnPróteinin MITF , TFEB, TFE3 og TFEC (stundum nefnd MiT-TFE þættirnir) tilheyra bHLHZip fjölskyldu umritunarþátta sem bindast DNA og stjórna tjáningu gena. MITF er mikilvægt fyrir myndun og starfsemi litfruma en ættingjar þess, TFEB og TFE3, stjórna myndun og starfsemi lysósóma og sjálfsáti. Sjálfsát er líffræðilegt ferli sem gegnir mikilvægu hlutverki í starfsemi fruma en getur einnig haft áHrif á myndun og meðHöndlun sjúkdóma. Í verkefni þessu var samstarf MITF, TFE3 og TFEB Próteinanna skoðað í sortuæxlisfrumum og hvaða áhrif þau Hafa á tjáningu hvers annars. Eins og MITF eru TFEB og TFE3 genin tjáð í sortuæxlisfrumum og sortuæxlum; TFEC er ekki tjáð í þessum frumum og var því ekki skoðað í þessu verkefni. Með notkun sérvirkra hindra var sýnt að boðleiðir hafa áhrif á staðsetningu próteinanna þriggja í sortuæxlisfrumum. Umritunarþættir þessir geta bundist skyldum DNA-bindisetum og haft áhrif á tjáningu gena sem eru nauðsynleg fyrir myndun bæði lýsósóma og melanósóma. -
Graft Versus Host Disease and How to Report It
Graft versus Host Disease and how to report it Daniel Weisdorf MD University of Minnesota Transplant Events Day-8 0 1mo 3mo 6mo Conditioning HSCT Engraftment Mucositis Organ toxicity (VOD) Acute GVHD Chronic GVHD Infections Bacterial ----CMV---- Varicella----- --Fungus--------- Transplant Events Day-8 0 1mo 3mo 6mo Conditioning HSCT Engraftment Mucositis Organ toxicity (VOD) Acute GVHD Chronic GVHD Infections Bacterial ----CMV---- Varicella----- --Fungus--------- 1 Acute GVHD Chronic GVHD Skin: Lichen planus, Hyper/ hypo pigmentation, Dermatitis ichthyosis, onychodystrophy, morphea, + scleroderma, hair changes. Hepatitis Oral: sicca, atrophy, lichenoid, + Hyperkeratosis GI: wasting, dysphagia, Enteritis odynophagia, strictures Eye: keratoconjunctivitis sicca Lungs: Bronchiolitis obliterans Others: myofascial, genital Acute GVHD Chronic GVHD Dermatitis Rash + Hepatitis High bilirubin + Enteritis Nausea/vomiting/ diarrhea Acute GVHD Chronic GVHD Skin: Lichen planus, Scaly abnormal pigmentation, Dry skin, onychodystrophy, abnormal nails scleroderma, thick skin hair changes. Oral: sicca, atrophy, lichenoid, Dry mouth GI: wasting, dysphagia, Weight loss odynophagia, trouble swallowing Eye: keratoconjunctivitis sicca Dry eyes Lungs: Bronchiolitis obliterans Obstruction Others: myofascial, muscle stiffness Genital vaginal narrowing 2 Graft vs. Leukemia Effect • Less leukemia relapse follows more GVHD • Acute and particularly Chronic GVHD limit relapse Risk Factors for GVHD Acute GVHD Chronic GVHD Increased risk Increased risk HLA mismatch Older -
Preconception Carrier Screening by Genome Sequencing: Results from the Clinical Laboratory
The American Journal of Human Genetics, Volume 102 Supplemental Data Preconception Carrier Screening by Genome Sequencing: Results from the Clinical Laboratory Sumit Punj, Yassmine Akkari, Jennifer Huang, Fei Yang, Allison Creason, Christine Pak, Amiee Potter, Michael O. Dorschner, Deborah A. Nickerson, Peggy D. Robertson, Gail P. Jarvik, Laura M. Amendola, Jennifer Schleit, Dana Kostiner Simpson, Alan F. Rope, Jacob Reiss, Tia Kauffman, Marian J. Gilmore, Patricia Himes, Benjamin Wilfond, Katrina A.B. Goddard, and C. Sue Richards Supplemental Note: Clinical Report Carrier Results: Four Known Pathogenic Variants Detected. Gene Inheritance Disease Prevalence Variant Classification Pendred Syndrome/ Non- syndromic Autosomal Hearing Loss A c.1246A>C, SLC26A4 1/500 Pathogenic Recessive DFNB4 with (p.Thr416Pro) enlarged vestibular aqueduct Autosomal Spastic ++ c.1045G>A, SPG7 2-6/100,000 Pathogenic Recessive Paraplegia 7 (p.Gly349Ser) 3.7 Autosomal Alpha +++ -α HBA2 1-5/10,000 Pathogenic Recessive Thalassemia (α+- thalassemia) Autosomal Hereditary 1/200 – c.845G>A HFE Pathogenic Recessive Hemochromatosis 1/1000+ (p.Cys282Tyr) +: GeneReviews; ++: Genetics Home Reference; +++: orphan.net – varies with population; A- Generalized prevalence of all deafness and hearing loss Interpretation: A sample from this individual was referred to our laboratory for analysis of Next-Generation Genome Sequencing (NGS) and Sanger confirmation of variants identified in carrier screening for: (1) conditions with significantly shortened lifespan; (2) serious conditions; (3) mild conditions; (4) conditions with unpredictable outcomes: and (5) conditions that begin as adults. One known heterozygous missense variant, c.1246A>C (p.Thr416Pro) (NM_000441.1), was detected in exon 10 of the SLC26A4 gene of this individual by NGS.