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Phenotypic heterogeneity

Gen Kano, Hisashi Tsujii, Kazuhiko Takeuchi, Kaname Nakatani, Makoto Ikejiri, Satoru Ogawa, Hisami Kubo, Mizuho Nagao, Takao Fujisawa
Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by structural and/or functional impairment of cilia throughout the whole body. Early diagnosis of PCD is important for the prevention of long‑term sequelae, however early diagnosis is a challenge due to the phenotypic heterogeneity of PCD. In the current study, the patient with PCD was diagnosed at nine years old following several efforts to control intractable airway symptoms. The patient experienced a chronic productive cough beginning in early childhood and had multiple episodes of pneumonia and otitis media with effusion and sinusitis...
October 21, 2016: Molecular Medicine Reports
Jia-Ze Tan, Yuan Man, Fei Xiao
BACKGROUND: Congenital myasthenic syndromes are a group of rare disorders that are clinically and genetically heterogeneous and caused by mutations in the genes encoding proteins of the neuromuscular junction. Here, we described a Chinese family that presented with phenotypes of classic slow-channel congenital myasthenic syndrome (SCCMS). METHODS: Clinical characteristics and electrophysiological features of three patients from a Chinese family were examined, and next-generation sequencing followed by direct sequencing was carried out...
2016: Chinese Medical Journal
Hong Ji, Jocelyn M Biagini Myers, Eric B Brandt, Cole Brokamp, Patrick H Ryan, Gurjit K Khurana Hershey
Exposure to traffic-related air pollution (TRAP) has been implicated in asthma development, persistence, and exacerbation. This exposure is highly significant as large segments of the global population resides in zones that are most impacted by TRAP and schools are often located in high TRAP exposure areas. Recent findings shed new light on the epigenetic mechanisms by which exposure to traffic pollution may contribute to the development and persistence of asthma. In order to delineate TRAP induced effects on the epigenome, utilization of newly available innovative methods to assess and quantify traffic pollution will be needed to accurately quantify exposure...
2016: Allergy, Asthma, and Clinical Immunology
Steven Walker, Anna C Bibby, Nick A Maskell
Malignant pleural effusions (MPEs) are an important cause of cancer-related mortality and morbidity. It is a heterogeneous group of conditions, which leads to debilitating symptoms and confers a poor prognosis. Recent well-designed randomized trials have provided a broader evidence base for an expanding range of treatment options. Together, with new prognostic scoring systems and a greater understanding of how different patient phenotypes respond to treatment, this allows greater personalization of management...
October 24, 2016: Therapeutic Advances in Respiratory Disease
Natalie S Ryan, Jennifer M Nicholas, Philip S J Weston, Yuying Liang, Tammaryn Lashley, Rita Guerreiro, Gary Adamson, Janna Kenny, Jon Beck, Lucia Chavez-Gutierrez, Bart de Strooper, Tamas Revesz, Janice Holton, Simon Mead, Martin N Rossor, Nick C Fox
BACKGROUND: The causes of phenotypic heterogeneity in familial Alzheimer's disease with autosomal dominant inheritance are not well understood. We aimed to characterise clinical phenotypes and genetic associations with APP and PSEN1 mutations in symptomatic autosomal dominant familial Alzheimer's disease (ADAD). METHODS: We retrospectively analysed genotypic and phenotypic data (age at symptom onset, initial cognitive or behavioural symptoms, and presence of myoclonus, seizures, pyramidal signs, extrapyramidal signs, and cerebellar signs) from all individuals with ADAD due to APP or PSEN1 mutations seen at the Dementia Research Centre in London, UK...
October 21, 2016: Lancet Neurology
Rachel S Kelly, Amber Dahlin, Michael J McGeachie, Weiliang Qiu, Joanne Sordillo, Emily S Wan, Ann Chen Wu, Jessica Lasky-Su
Asthma is a complex disease well suited to metabolomic profiling, both for the development of novel biomarkers and for the improved understanding of pathophysiology. In this review, we summarize the 21 existing metabolomic studies of asthma in humans, all of which reported significant findings and concluded that individual metabolites and metabolomic profiles measured in exhaled breath condensate, urine, plasma and serum could identify asthmatics and asthma phenotypes with high discriminatory ability. There was considerable consistency across the studies in terms of the reported biomarkers, regardless of biospecimen, profiling technology and population age...
October 21, 2016: Chest
Sallie Baxendale, Pamela Thompson
The revised terminology and concepts for the organization of seizures and epilepsy proposed by the ILAE Commission on Classification and Terminology in 2010 allows for a number of new opportunities in the study of cognition and behavior in adults. This review examines the literature that has looked for behavioral and cognitive correlates of the newly recognized genetic epilepsies in adults. While some studies report clear cognitive phenotypes associated with specific genetic mutations in adults with epilepsy, others report remarkable clinical heterogeneity...
October 21, 2016: Epilepsy & Behavior: E&B
Akshay Shekhar, Xianming Lin, Fang-Yu Liu, Jie Zhang, Huan Mo, Lisa Bastarache, Joshua C Denny, Nancy J Cox, Mario Delmar, Dan M Roden, Glenn I Fishman, David S Park
Rapid impulse propagation in the heart is a defining property of pectinated atrial myocardium (PAM) and the ventricular conduction system (VCS) and is essential for maintaining normal cardiac rhythm and optimal cardiac output. Conduction defects in these tissues produce a disproportionate burden of arrhythmic disease and are major predictors of mortality in heart failure patients. Despite the clinical importance, little is known about the gene regulatory network that dictates the fast conduction phenotype. Here, we have used signal transduction and transcriptional profiling screens to identify a genetic pathway that converges on the NRG1-responsive transcription factor ETV1 as a critical regulator of fast conduction physiology for PAM and VCS cardiomyocytes...
October 24, 2016: Journal of Clinical Investigation
Damjan Glavač, Martina Jarc-Vidmar, Katarina Vrabec, Metka Ravnik-Glavač, Ana Fakin, Marko Hawlina
PURPOSE: To determine the spectrum of BEST1 mutations and to study the phenotype in Slovenian families with Best vitelliform macular dystrophy (BVMD) to identify genotype-phenotype correlations. METHODS: Twenty patients from five families underwent the ophthalmological examination including electrooculogram (EOG; N = 17), fundus autofluorescence imaging (N = 16) and optical coherence tomography (N = 14). Mutational screening was performed by direct DNA sequencing of the BEST1 gene...
October 24, 2016: Acta Ophthalmologica
Mazen Al-Hommrani, Paramita Chakraborty, Shilpak Chatterjee, Shikhar Mehrotra
Cell, the basic unit of life depends for its survival on nutrients and thereby energy to perform its physiological function. Cells of lymphoid and myeloid origin are key in evoking an immune response against "self" or "non-self" antigens. The thymus derived lymphoid cells called T cells are a heterogenous group with distinct phenotypic and molecular signatures that have been shown to respond against an infection (bacterial, viral, protozoan) or cancer. Recent studies have unearthed the key differences in energy metabolism between the various T cell subsets, natural killer cells, dendritic cells, macrophages and myeloid derived suppressor cells...
2016: J Immunol Res Ther
Valerie J Morley, Mark Sistrom, Jose A Usme-Ciro, Susanna K Remold, Paul E Turner
Virus populations may be challenged to evolve in spatially heterogeneous environments, such as mixtures of host cells that pose differing selection pressures. Spatial heterogeneity may select for evolved polymorphisms, where multiple virus subpopulations coexist by specializing on a narrow subset of the available hosts. Alternatively, spatial heterogeneity may select for evolved generalism, where a single genotype dominates the virus population by occupying a relatively broader host niche. In addition, the extent of spatial heterogeneity should influence the degree of divergence among virus populations encountering identical environmental challenges...
January 2016: Virus Evolution
Diane Lefaudeux, Bertrand De Meulder, Matthew J Loza, Nancy Peffer, Anthony Rowe, Frédéric Baribaud, Aruna T Bansal, Rene Lutter, Ana R Sousa, Julie Corfield, Ioannis Pandis, Per S Bakke, Massimo Caruso, Pascal Chanez, Sven-Erik Dahlén, Louise J Fleming, Stephen J Fowler, Ildiko Horvath, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandstrom, Dominic E Shaw, Florian Singer, Peter J Sterk, Graham Roberts, Ian M Adcock, Ratko Djukanovic, Charles Auffray, Kian F Chung
BACKGROUND: Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalised management approach can be provided. OBJECTIVES: We stratified patients with moderate-to-severe asthma based on clinico-physiological parameters and performed an -omics analysis of sputum. METHODS: Partition-around-medoid clustering was applied to a training set of 266 asthma participants from the European U-BIOPRED adult cohort using 8 pre-specified clinic-physiological variables...
October 20, 2016: Journal of Allergy and Clinical Immunology
Maxim N Artyomov, Alexey Sergushichev, Joel D Schilling
Macrophages are heterogeneous cells that play a key role in inflammatory and tissue reparative responses. Over the past decade it has become clear that shifts in cellular metabolism are important determinants of macrophage function and phenotype. At the same time, our appreciation of macrophage diversity in vivo has also been increasing. Factors such as cell origin and tissue localization are now recognized as important variables that influence macrophage biology. Whether different macrophage populations also have unique metabolic phenotypes has not been extensively explored...
October 19, 2016: Seminars in Immunology
Violeta N Kovacheva, Nasir M Rajpoot
BACKGROUND: New bioimaging techniques capable of visualising the co-location of numerous proteins within individual cells have been proposed to study tumour heterogeneity of neighbouring cells within the same tissue specimen. These techniques have highlighted the need to better understand the interplay between proteins in terms of their colocalisation. RESULTS: We recently proposed a cellular-level model of the healthy and cancerous colonic crypt microenvironments...
October 22, 2016: BMC Bioinformatics
Paresh Zanzmera, Ramshekhar N Menon, Kalyani Karkare, Himanshu Soni, Sujit Jagtap, Ashalatha Radhakrishnan
PURPOSE: The purpose of this article was to study the electroclinical characteristics and seizure outcome of children with epilepsy with myoclonic absences (EMA). METHOD: In this descriptive cohort study, we reviewed clinical records of patients who met the criteria for EMA. Each patient's demographic data, birth/developmental history, seizure semiology/pattern, antiepileptic drugs (AED), clinical examination, video-electroencephalography (VEEG), and neuroimaging data were reviewed...
October 19, 2016: Epilepsy & Behavior: E&B
Daniel Nichol, Mark Robertson-Tessi, Peter Jeavons, Alexander R A Anderson
Non-genetic variation in phenotypes, or bet-hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet-hedging emerges in the genotype-phenotype mapping through a simple interaction model: a molecular switch. We use simple Chemical Reaction Networks to implement stochastic switches that map gene products to phenotypes and investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet-hedging naturally emerges within this model and is robust to evolutionary loss through mutations to both the expression of individual genes and to the network itself...
October 21, 2016: Genetics
Lauren E Griffith, Edwin van den Heuvel, Parminder Raina, Isabel Fortier, Nazmul Sohel, Scott M Hofer, Hélène Payette, Christina Wolfson, Sylvie Belleville, Meghan Kenny, Dany Doiron
Standardization procedures are commonly used to combine phenotype data that were measured using different instruments, but there is little information on how the choice of standardization method influences pooled estimates and heterogeneity. Heterogeneity is of key importance in meta-analyses of observational studies because it affects the statistical models used and the decision of whether or not it is appropriate to calculate a pooled estimate of effect. Using 2-stage individual participant data analyses, we compared 2 common methods of standardization, T-scores and category-centered scores, to create combinable memory scores using cross-sectional data from 3 Canadian population-based studies (the Canadian Study on Health and Aging (1991-1992), the Canadian Community Health Survey on Healthy Aging (2008-2009), and the Quebec Longitudinal Study on Nutrition and Aging (2004-2005))...
October 21, 2016: American Journal of Epidemiology
Nadia A Akawi, Salma Ben-Salem, Jozef Hertecant, Anne John, Thachillath Pramathan, Praseetha Kizhakkedath, Bassam R Ali, Lihadh Al-Gazali
BACKGROUND: The group of ELAC2-related encephalomyopathies is a recent addition to the rapidly growing heterogeneous mitochondrial disorders. RESULTS: We describe a highly inbred consanguineous Pakistani family with multiple affected children in 2 branches exhibiting moderately severe global developmental delay. Using homozygosity mapping, we mapped the phenotype in this family to a single locus on chromosome 17. In addition, whole-exome sequencing identified a homozygous splicing mutation (c...
October 21, 2016: Orphanet Journal of Rare Diseases
Deying Liu, Jinxiang Liu, Jinghua Wang, Congcong Liu, Sirui Yang, Yanfang Jiang
BACKGROUND: Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4(+) helper T cells that promotes pathogenic immune responses in autoimmune diseases. In this study, we examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA vasculitis (IgAV). METHODS: According to the phenotypic expressions of different molecules, focus was given on six subpopulations of Tfh cells: CD4(+)CXCR5(+), CD4(+)CXCR5(+)ICOS(+), CD4(+)CXCR5(+)ICOS(+)PD-1(+), CD4(+)CXCR5(+)ICOS(high)PD-1(high), CD4(+)CXCR5(+)ICOS(-)PD-1(+), and CXCR5(+)CD45RA(-)IL-21(+)...
October 21, 2016: BMC Immunology
Malik Nassan, Qingqin Li, Paul E Croarkin, Wenan Chen, Colin L Colby, Marin Veldic, Susan L McElroy, Gregory D Jenkins, Euijung Ryu, Julie M Cunningham, Marion Leboyer, Mark A Frye, Joanna M Biernacka
BACKGROUND: Although multiple genes have been implicated in bipolar disorder (BD), they explain only a small proportion of its heritability. Identifying additional BD risk variants may be impaired by phenotypic heterogeneity, which is usually not taken into account in genome-wide association studies (GWAS). BD with early age at onset is a more homogeneous familial form of the disorder associated with greater symptom severity. METHODS: We conducted a GWAS of early-onset BD (onset of mania/hypomania ≤19 years old) in a discovery sample of 419 cases and 1034 controls and a replication sample of 181 cases and 777 controls...
September 30, 2016: Journal of Affective Disorders
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