scholarly journals Identification of Two Dysfunctional Variants in the ABCG2 Urate Transporter Associated with Pediatric-Onset of Familial Hyperuricemia and Early-Onset Gout

2021 ◽  
Vol 22 (4) ◽  
pp. 1935
Author(s):  
Yu Toyoda ◽  
Kateřina Pavelcová ◽  
Jana Bohatá ◽  
Pavel Ješina ◽  
Yu Kubota ◽  
...  
Keyword(s):  
Early Onset ◽  
Molecular Genetic ◽  
Clinical Information ◽  
Clinical History ◽  
Coding Region ◽  
Factors Affecting ◽  
Functional Studies ◽  
Urate Transporter ◽  
History Of ◽  
Pediatric Onset

The ABCG2 gene is a well-established hyperuricemia/gout risk locus encoding a urate transporter that plays a crucial role in renal and intestinal urate excretion. Hitherto, p.Q141K—a common variant of ABCG2 exhibiting approximately one half the cellular function compared to the wild-type—has been reportedly associated with early-onset gout in some populations. However, compared with adult-onset gout, little clinical information is available regarding the association of other uricemia-associated genetic variations with early-onset gout; the latent involvement of ABCG2 in the development of this disease requires further evidence. We describe a representative case of familial pediatric-onset hyperuricemia and early-onset gout associated with a dysfunctional ABCG2, i.e., a clinical history of three generations of one Czech family with biochemical and molecular genetic findings. Hyperuricemia was defined as serum uric acid (SUA) concentrations 420 μmol/L for men or 360 μmol/L for women and children under 15 years on two measurements, performed at least four weeks apart. The proband was a 12-year-old girl of Roma ethnicity, whose SUA concentrations were 397–405 µmol/L. Sequencing analyses focusing on the coding region of ABCG2 identified two rare mutations—c.393G>T (p.M131I) and c.706C>T (p.R236X). Segregation analysis revealed a plausible link between these mutations and hyperuricemia and the gout phenotype in family relatives. Functional studies revealed that p.M131I and p.R236X were functionally deficient and null, respectively. Our findings illustrate why genetic factors affecting ABCG2 function should be routinely considered in clinical practice as part of a hyperuricemia/gout diagnosis, especially in pediatric-onset patients with a strong family history.

scholarly journals New challenges in evaluating anemia in older persons in the era of molecular testing

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 67-73 ◽  
Author(s):  
David P. Steensma
Keyword(s):  
Natural History ◽  
Older Persons ◽  
Molecular Genetic ◽  
Clinical History ◽  
The Elderly ◽  
Molecular Testing ◽  
Myeloid Neoplasm ◽  
Hematologic Neoplasm ◽  
History Of ◽  
Clonal Mutation

Abstract Anemia is common in older persons, and often remains unexplained despite a thorough clinical history, physical examination, and focused laboratory testing, including marrow aspiration, biopsy, and karyotyping. The advent of molecular genetic testing panels in hematology clinical practice has complicated the evaluation of older patients with unexplained anemia. While the presence of a somatic mutation provides evidence of clonal hematopoiesis and may support a diagnosis of a hematologic neoplasm such as one of the myelodysplastic syndromes (MDS), with rare exceptions, individual mutations are not strongly associated with one specific diagnosis, nor are they by themselves diagnostic of neoplasia. A clonal mutation in a patient with cytopenias and a nondiagnostic bone marrow may indicate a syndrome with a similar natural history to MDS, but at present there are no clear criteria to distinguish cytopenias coincidentally seen in association with an unrelated clonal mutation from cytopenias that are directly caused by that mutation. Ongoing and planned analyses will help define when mutation patterns alone can identify a disorder equivalent to a morphologically defined myeloid neoplasm such as MDS, further clarifying the etiology and natural history of unexplained anemia in the elderly.

scholarly journals New Genes from Old: Redeployment of dUTPase by Herpesviruses

2005 ◽  
Vol 79 (20) ◽  
pp. 12880-12892 ◽  
Author(s):  
Andrew J. Davison ◽  
Nigel D. Stow
Keyword(s):  
Evolutionary History ◽  
Human Herpesvirus ◽  
Duplication Event ◽  
Coding Region ◽  
Conserved Residues ◽  
Herpesvirus 8 ◽  
Functional Studies ◽  
New Genes ◽  
History Of ◽  
Sequence Similarities

ABSTRACT Published work (D. J. McGeoch, Nucleic Acids Res. 18:4105-4110, 1990; J. E. McGeehan, N. W. Depledge, and D. J. McGeoch, Curr. Protein Peptide Sci. 2:325-333, 2001) has indicated that evolution of dUTPase in the class of herpesviruses that infect mammals and birds involved capture of a host gene followed by a duplication event that resulted in a coding region comprising two fused dUTPase domains. Some of the conserved residues required for enzyme activity were then lost, resulting in a dUTPase containing a single active site with different elements contributed by each half of the protein. Further conserved residues were lost in one subfamily (the Betaherpesvirinae), yielding a protein that is related to herpesvirus dUTPases but has a different and as yet unrecognized function. Evidence from sequence similarities and structural predictions now indicates that several additional genes were derived from the herpesvirus dUTPase gene, probably by duplication. These are UL31, UL82, UL83, and UL84 in human cytomegalovirus (and counterparts in other members of the Betaherpesvirinae) and ORF10 and ORF11 in human herpesvirus 8 (and counterparts in other members of the Gammaherpesvirinae). The findings clarify the evolutionary history of these genes and provide novel insights for structural and functional studies.

scholarly journals Genetic evaluation for TOR1-A (DYT1) in Brazilian patients with dystonia

2014 ◽  
Vol 72 (10) ◽  
pp. 753-756 ◽  
Author(s):  
Carlos Henrique F. Camargo ◽  
Sarah Teixeira Camargos ◽  
Salmo Raskin ◽  
Francisco Eduardo C. Cardoso ◽  
Hélio Afonso G. Teive
Keyword(s):  
Movement Disorders ◽  
Early Onset ◽  
Gene Mutations ◽  
Clinical Information ◽  
Familial History ◽  
Dyt1 Gene ◽  
History Of ◽  
Sporadic Cases ◽  
Cervical Area ◽  
Secondary Generalization

Several genes have been mapped in families or in sporadic cases of dystonia. TOR1-A (DYT1) gene was linked to isolated dystonia. Objective To associate clinical information of patients with dystonia with the TOR1-A gene mutations. Method Eighty-eight patients with dystonia in cervical area (focal, segmental, multifocal and generalized) were recruited at Movement Disorders Clinic of Hospital de Clínicas of the Federal University of Paraná between June of 2008 and June of 2009. They were submitted to the clinical evaluation. DNA was extract from blood and submitted at analysis to TOR1-A mutations by PCR according standard protocols. Results Two patients had c.907GAGdel mutation on TOR1-A gene. These patients, with familial history of dystonia, started his symptoms by legs and had secondary generalization. Conclusion We can suggest that analysis for TOR1-A mutations should be performed only in patients with early onset, generalized and familial dystonia.

scholarly journals Reply to Drs. Kiaei and Molinaro Regarding the Publication “Comparison of a Bridge Immunoassay with Two Bioassays for Thyrotropin Receptor Antibody Detection and Differentiation”

2020 ◽  
Vol 52 (02) ◽  
pp. 126-127
Author(s):  
Stephanie Allelein ◽  
Tanja Diana ◽  
Matthias Schott ◽  
George J. Kahaly
Keyword(s):  
Package Insert ◽  
Clinical Information ◽  
Clinical History ◽  
Physical Symptoms ◽  
Antibody Detection ◽  
American Thyroid Association ◽  
Test Results ◽  
Thyrotropin Receptor Antibody ◽  
History Of ◽  
Drug Treatments

Dear Editor,Drs. Kiaei and Molinaro 1 put forth two criticisms of the manuscript published by us 2. They state that the experimental design of this study is flawed and that the authors falsely claim that negative Thyretain™ TSI Reporter BioAssay results for two Graves’ diseases patients undergoing drug treatments means the absence of stimulating antibodies. To substantiate this claim Drs. Kiaei and Molinaro point out that the manufacturer of the Thyretain TSI Reporter BioAssay clearly states in the package insert that “[t]he effects of various drug therapies on the performance of this Kit have not been established” 1. Second, the package insert explicitly states that “[a] negative result does not exclude the possibility of the presence of TSI” and results of the test should be interpreted in conjunction with information available from other clinical information, such as physical symptoms and thyroid hormone testing, as recommended by the American Thyroid Association (ATA)”. Furthermore they state that the “authors of the manuscript did not consider the manufacturer’s warning regarding the intended patient population and the ATA guidelines regarding the interpretation of the test results in conjunction with other clinical information. Instead, the authors based their conclusions on the negative Thyretain TSI Reporter BioAssay results and ignored the patients’ clinical history of Graves’ disease.”

Component resolved diagnostics in peanut sensitized children with and without a history of clinical reaction

2020 ◽  
Vol 41 (5) ◽  
pp. 336-340
Author(s):  
Yasmin Hamzavi Abedi ◽  
Cristina P. Sison ◽  
Punita Ponda
Keyword(s):  
Retrospective Chart Review ◽  
Clinical History ◽  
Specific Ige ◽  
Exact Test ◽  
Ara H 1 ◽  
Sige Level ◽  
History Of ◽  
Laboratory Procedures ◽  
Ige Mediated ◽  
The Relationship

Background: Serum Peanut-specific-IgE (PN-sIgE) and peanut-component-resolved-diagnostics (CRD) are often ordered simultaneously in the evaluation for peanut allergy. Results often guide the plans for peanut oral challenge. However, the clinical utility of CRD at different total PN-sIgE levels is unclear. A commonly used predefined CRD Ara h2 cutoff value in the literature predicting probability of peanut challenge outcomes is 0.35kUA/L. Objective: To examine the utility of CRD in patients with and without a history of clinical reactivity to peanut (PN). Methods: This was a retrospective chart review of 196 children with PN-sIgE and CRD testing, of which, 98 patients had a clinical history of an IgE-mediated reaction when exposed to PN and 98 did not. The Fisher's exact test was used to assess the relationship between CRD and PN-sIgE at different cutoff levels, McNemar test and Gwet’s approach (AC1 statistic) were used to examine agreement between CRD and PN-sIgE, and logistic regression was used to assess differences in the findings between patients with and without reaction history. Results: Ara h 1, 2, 3, or 9 (ARAH) levels ≤0.35 kUA/L were significantly associated with PN-sIgE levels <2 kUA/L rather than ≥2 kUA/L (p < 0.0001). When the ARAH threshold was increased to 1 kUA/L and 2 kUA/L, these thresholds were still significantly associated with PN-sIgE levels of <2, <5, and <14 kUA/L. These findings were not significantly different in patients with and without a history of clinical reactivity. Conclusion: ARAH values correlated with PN-sIgE. Regardless of clinical history, ARAH levels are unlikely to be below 0.35, 1, or 2 kUA/L if the PN-sIgE level is >2 kUA/L. Thus, if possible, practitioners should consider PN-sIgE rather than automatically ordering CRD with PN-sIgE every time. Laboratory procedures that allow automatically and reflexively adding CRD when the PN-sIgE level is ≤5 kUA/L can be helpful. However, further studies are needed in subjects with challenge-proven PN allergy.

Stepping up detection, response, preparedness and readiness measures for “COVID-19”- A Pandemic

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1042-1047
Author(s):  
Khushbu Balsara ◽  
Deepankar Shukla
Keyword(s):  
Health Care ◽  
Health Care Workers ◽  
Clinical History ◽  
Frontline Workers ◽  
Diagnostic Assays ◽  
Care Workers ◽  
Short Period ◽  
History Of ◽  
Detection Response ◽  
Care Worker

In a very short period of time, “COVID-19” has seized the consciousness globally by making remarkable changes in our day to day living and has superintended as a public health emergency globally. It has high radar of transmission, affecting an individual at work to frontline workers. The measures and planning for a response plays a key role from drawing up an emergency committee and this follows an equation which broadly deals with epidemiological to clinical history of the patient, management steps from isolation, screening, diagnostic assays for identification and treatment. The application of an organized plan with secure structure aids in better performance, increases efficacy of management and saves time. Also saves time for a health care worker to g through routine levels of channels of administration if already a familiar way of operation is known for such situations. Thus, planning and developing a ‘blueprint of approach’ towards management of patient while facing such situation is a must. This review provides an insight to the measures for detection, response and preparedness of the hospital and health care workers should largely be inclusive of; also highlights the measures to be taken at every step after coming in contact with a positive case of “COVID-19”.

Gene mutation and drug resistance of M. tuberculosis in the patients followed up in the city of Moscow

2020 ◽  
Vol 97 (12) ◽  
pp. 34-44
Author(s):  
M. A. Krasnova ◽  
E. M. Belilovsky ◽  
S. E. Borisov ◽  
A. A. Khakhalina ◽  
Yu. D. Mikhaylova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Statistical Significance ◽  
Molecular Genetic ◽  
Previous Treatment ◽  
Repeated Treatment ◽  
Phenotypic Resistance ◽  
Therapy Regimen ◽  
Treatment History ◽  
History Of ◽  
Relationship Of

The article describes a retrospective study of the results of microbiological and molecular genetic tests of 685 M. tuberculosis cultures isolated from 685 adult tuberculosis patients registered for dispensary follow-up in Moscow in 2014.The following was identified during the study: phenotypic drug resistance (FDR) of MTB to rifampicin, isoniazid, fluoroquinolones, kanamycin, amikacin, and capreomycin in groups of patients with different treatment history; the frequency of FDR to the above anti-tuberculosis drugs in strains with mutations being drug resistance markers; the frequency of various mutations in case of FDR of mycobacteria in the patients from different groups; the relationship of FDR or the presence of a particular mutation with various characteristics of the patients and their treatment history.The history of previous treatment was determined as statistical significance to provide the greatest influence on the spread of drug resistant MTB: patients undergoing repeated treatment had FDR more often and also a much more pronounced variety of mutations being markers of FDR to certain anti-tuberculosis drugs.The results of the study showed that the detection of genetic mutations in MBT associated with FDR was a reliable tool for predicting phenotypic resistance and should be used as the main method for selecting anti-tuberculosis drugs when compiling the etiotropic therapy regimen.

An overview of Osmotic Drug Delivery System: An update review

2017 ◽  
Vol 6 (7) ◽  
pp. 5426 ◽  
Author(s):  
Hiren J. Patel ◽  
Vaishnavi P. Parikh
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Life Cycle Management ◽  
Delivery Systems ◽  
Osmotic Pump ◽  
Factors Affecting ◽  
Advantages And Disadvantages ◽  
New Chemical Entities ◽  
History Of ◽  
Novel Drug

The pharmaceutical industry has faced several marked challenges in order to bring new chemical entities (NCEs) into the market over the past few decades. Various novel drug delivery approaches have been used as a part of life cycle management from which Osmotic drug delivery systems look the most promising one. After discussing the history of osmotic pump development, this article looks at the principles, advantages and disadvantages of osmotic drug delivery systems. Then, the basic components of osmotic pump and factors affecting the design of oral osmotic drug delivery systems are discussed in detail. In the later part of the manuscript, various types of osmotic pumps available in the market and evaluation methods for osmotic drug delivery systems are discussed in detail.

scholarly journals Persistent vegetative state: an overview

2021 ◽  
Vol 36 (1) ◽  
Author(s):  
Gabriel Alexander Quiñones-Ossa ◽  
Yeider A. Durango-Espinosa ◽  
Tariq Janjua ◽  
Luis Rafael Moscote-Salazar ◽  
Amit Agrawal
Keyword(s):  
Intensive Care ◽  
Vegetative State ◽  
Persistent Vegetative State ◽  
Clinical History ◽  
Main Body ◽  
Disorder Of Consciousness ◽  
Family Perspective ◽  
Patient Status ◽  
History Of ◽  
State Diagnosis

Abstract Background Disorder of consciousness diagnosis, especially when is classified as persistent vegetative state (without misestimating the other diagnosis classifications), in the intensive care is an important diagnosis to evaluate and treat. Persistent vegetative state diagnosis is a challenge in the daily clinical practice because the diagnosis is made mainly based upon the clinical history and the patient behavior observation. There are some specific criteria for this diagnosis, and this could be very tricky when the physician is not well trained. Main body We made a literature review regarding the persistent vegetative state diagnosis, clinical features, management, prognosis, and daily medical practice challenges while considering the bioethical issues and the family perspective about the patient status. The objective of this overview is to provide updated information regarding this clinical state’s features while considering the current medical literature available. Conclusions Regardless of the currently available guidelines and literature, there is still a lot of what we do not know about the persistent vegetative state. There is a lack of evidence regarding the optimal diagnosis and even more, about how to expect a natural history of this disorder of consciousness. It is important to recall that the patients (despite of their altered mental state diagnosis) should always be treated to avoid some of the intensive care unit long-stance complications.

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