Selective screening and molecular characteristics of Russian patients with Pompe disease

2021 ◽  
Vol 2 (4) ◽  
pp. 203-215
Author(s):  
Kirill V. Savostyanov ◽  
Alexander A. Pushkov ◽  
Elena N. Basargina ◽  
Lyudmila M. Kuzenkova ◽  
Natalia N. Mazanova ◽  
...  
Keyword(s):  
Pompe Disease ◽  
High Performance ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Risk Groups ◽  
Laboratory Diagnosis ◽  
The Body ◽  
Molecular Characteristics ◽  
Selective Screening ◽  
Gaa Gene

Introduction. Pompe disease (PD) or type II glycogenosis is a rare multisystem hereditary accumulation disease caused by a deficiency of the enzyme acid maltase (acid alpha-1,4-glucosidase), which leads to reduced activity to the accumulation of glycogen in various organs and tissues of the body. The aim of the study is to develop a high-performance method of early biochemical diagnosis of PD and optimization of its molecular genetic diagnosis. Materials and methods. The characteristics of the relative frequencies and spectrum of the detected mutations were studied using a sample of 7670 patients with suspected Pompe disease admitted to the National Medical Research Center of Children’s Health of the Ministry of Health of Russia as part of the selective screening, as well as eight patients with PD, whose laboratory diagnosis was made outside the framework of this selective screening. Results. As a result of selective screening of PD in Russian patients from high-risk groups, the detectability was 0.47%. PD’s clinical and age characteristics in both children and adults are described. The relative frequencies are calculated, and the spectrum of 47 pathogenic variants of the GAA gene responsible for the occurrence and development of Pompe disease in 44 patients is characterized. Seventeen new mutations of the GAA gene, unknown previously, have been identified and described, adding 2.7% to the HGMD database. Conclusion. Optimization of the algorithm of molecular diagnosis of Pompe disease in Russian patients is proposed.

scholarly journals Genetic predisposition and resistance to certain infectious diseases. I. AIDS

2019 ◽  
Vol 3 (22) ◽  
pp. 6-10
Author(s):  
S. N. Shcherbo ◽  
D. S. Shcherbo ◽  
A. L. Tishchenko ◽  
M. I. Savina ◽  
T. I. Turkina
Keyword(s):  
Infectious Diseases ◽  
Genetic Predisposition ◽  
Molecular Genetic ◽  
Risk Groups ◽  
The Body ◽  
Genetic Biomarkers ◽  
Histocompatibility Complex ◽  
Tick Borne Encephalitis ◽  
Main Influence

The review addresses issues related to genetic predisposition and resistance to infectious diseases. Genetic factors largely determine the susceptibility of the body to various diseases, including infectious ones. A genetic predisposition to tuberculosis, salmonellosis, viral hepatitis, tick-borne encephalitis, Lyme disease, HIV and others is shown. Knowledge of molecular genetic biomarkers is necessary for identifying risk groups, conducting predictive measures, in particular vaccination. The main influence is given to the genes of the main histocompatibility complex; the role of mitochondrial DNA in susceptibility to HIV infection is shown.

scholarly journals Complex Transposon Insertion as a Novel Cause of Pompe Disease

2021 ◽  
Vol 22 (19) ◽  
pp. 10887
Author(s):  
Igor Bychkov ◽  
Galina Baydakova ◽  
Alexandra Filatova ◽  
Ochir Migiaev ◽  
Andrey Marakhonov ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Autosomal Recessive ◽  
Mobile Genetic Element ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Lysosomal Storage ◽  
Pathogenic Variants ◽  
Transposon Insertion ◽  
Gaa Gene ◽  
Mutation Databases

Pompe disease (OMIM#232300) is an autosomal recessive lysosomal storage disorder caused by mutations in the GAA gene. According to public mutation databases, more than 679 pathogenic variants have been described in GAA, none of which are associated with mobile genetic elements. In this article, we report a novel molecular genetic cause of Pompe disease, which could be hardly detected using routine molecular genetic analysis. Whole genome sequencing followed by comprehensive functional analysis allowed us to discover and characterize a complex mobile genetic element insertion deep in the intron 15 of the GAA gene in a patient with infantile onset Pompe disease.

scholarly journals Genetic predisposition and resistance to certain infectious diseases. II. Sexually transmitted infections

2020 ◽  
pp. 5-8
Author(s):  
S. N. Scherbo ◽  
D. S. Shcherbo ◽  
A. L. Tishchenko ◽  
M. I. Savina ◽  
T. I. Turkina
Keyword(s):  
Sexually Transmitted Infections ◽  
Genetic Predisposition ◽  
Molecular Genetic ◽  
Risk Groups ◽  
The Body ◽  
Sexually Transmitted ◽  
Genetic Biomarkers ◽  
Histocompatibility Complex ◽  
Clinical Consequences ◽  
Main Influence

The review addresses issues related to genetic predisposition and resistance to sexually transmitted infections (STI). Genetic factors largely determine the susceptibility of the body to various diseases, including infectious ones. The main influence is given to the genes of the main histocompatibility complex and toll-like receptors. Some STI and genetic polymorphisms responsible for resistance and susceptibility to infections and related clinical consequences are considered. Knowledge of molecular genetic biomarkers is necessary to identify risk groups, conduct predictive measures, in particular vaccination.

ANALYSIS OF ABDOMINAL TYPHOID INCIDENCE IN THE SOUTH REGION OF THE KYRGYZ REPUBLIC

2020 ◽  
pp. 43-48
Author(s):  
Zakirova J.S. ◽  
Nadirbekova R.A. ◽  
Zholdoshev S.T.
Keyword(s):  
Drinking Water ◽  
Typhoid Fever ◽  
Risk Groups ◽  
The Body ◽  
Kyrgyz Republic ◽  
Radiation Factor ◽  
High Quality ◽  
Two Generations ◽  
Immunological Deficiency

The article analyze the long-term morbidity, spread of typhoid fever in the southern regions of the Kyrgyz republic, and remains a permanent epidemic focus in the Jalal-Abad region, where against the low availability of the population to high-quality drinking water, an additional factor on the body for more than two generations and radiation factor, which we confirmed by the spread among the inhabitants of Mailuu-Suu of nosological forms of the syndrome of immunological deficiency, as a predictor of risk groups for infectious diseases, including typhoid fever.

Evaluation of New 99mTc(CO)3 + Radiolabeled Glycylglycine In Vivo

2019 ◽  
Vol 19 (11) ◽  
pp. 1382-1387
Author(s):  
Ahmet M. Şenışık ◽  
Çiğdem İçhedef ◽  
Ayfer Y. Kılçar ◽  
Eser Uçar ◽  
Kadir Arı ◽  
...  
Keyword(s):  
High Performance ◽  
The Body ◽  
Biological Behavior ◽  
In Vivo Evaluation ◽  
Radiolabeled Peptides ◽  
Tumor Bearing ◽  
Biodistribution Data ◽  
Good Accordance ◽  
Rapid Clearance

Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [99mTc(CO)3(H2O)3]+ radiolabeled glycylglycine (GlyGly). Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex (99mTc(CO)3-Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging. Results: The high radiolabelling yield of 99mTc(CO)3-GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal. Conclusion: This study shows that 99mTc(CO)3-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99mTc(CO)3-GlyGly can be performed on tumor-bearing animals.

scholarly journals Calculating the optimal hematocrit under the constraint of constant cardiac power

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michal Sitina ◽  
Heiko Stark ◽  
Stefan Schuster
Keyword(s):  
Blood Flow ◽  
High Performance ◽  
Animal Species ◽  
Normal Values ◽  
Mechanical Load ◽  
The Body ◽  
Trade Off ◽  
Cardiac Power ◽  
Optimal Value ◽  
Good Agreement

AbstractIn humans and higher animals, a trade-off between sufficiently high erythrocyte concentrations to bind oxygen and sufficiently low blood viscosity to allow rapid blood flow has been achieved during evolution. Optimal hematocrit theory has been successful in predicting hematocrit (HCT) values of about 0.3–0.5, in very good agreement with the normal values observed for humans and many animal species. However, according to those calculations, the optimal value should be independent of the mechanical load of the body. This is in contradiction to the exertional increase in HCT observed in some animals called natural blood dopers and to the illegal practice of blood boosting in high-performance sports. Here, we present a novel calculation to predict the optimal HCT value under the constraint of constant cardiac power and compare it to the optimal value obtained for constant driving pressure. We show that the optimal HCT under constant power ranges from 0.5 to 0.7, in agreement with observed values in natural blood dopers at exertion. We use this result to explain the tendency to better exertional performance at an increased HCT.

scholarly journals PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8298
Author(s):  
Hugo Christian Monroy-Ramirez ◽  
Marina Galicia-Moreno ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Arturo Santos ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Metabolic Regulation ◽  
Structural Changes ◽  
Critical Role ◽  
The Body ◽  
Molecular Characteristics ◽  
Signal Pathways ◽  
Virus Infections ◽  
Physiological Processes ◽  
Hepatic Level

Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development.

scholarly journals Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fiona Li ◽  
Justin W. Hicks ◽  
Lihai Yu ◽  
Lise Desjardin ◽  
Laura Morrison ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Blood Plasma ◽  
Kinetic Parameters ◽  
High Performance ◽  
The Body ◽  
Accurate Estimation ◽  
Dynamic Pet ◽  
Arterial Concentration ◽  
In Blood Plasma

Abstract Background In molecular imaging with dynamic PET, the binding and dissociation of a targeted tracer is characterized by kinetics modeling which requires the arterial concentration of the tracer to be measured accurately. Once in the body the radiolabeled parent tracer may be subjected to hydrolysis, demethylation/dealkylation and other biochemical processes, resulting in the production and accumulation of different metabolites in blood which can be labeled with the same PET radionuclide as the parent. Since these radio-metabolites cannot be distinguished by PET scanning from the parent tracer, their contribution to the arterial concentration curve has to be removed for the accurate estimation of kinetic parameters from kinetic analysis of dynamic PET. High-performance liquid chromatography has been used to separate and measure radio-metabolites in blood plasma; however, the method is labor intensive and remains a challenge to implement for each individual patient. The purpose of this study is to develop an alternate technique based on thin layer chromatography (TLC) and a sensitive commercial autoradiography system (Beaver, Ai4R, Nantes, France) to measure radio-metabolites in blood plasma of two targeted tracers—[18F]FAZA and [18F]FEPPA, for imaging hypoxia and inflammation, respectively. Results Radioactivity as low as 17 Bq in 2 µL of pig’s plasma can be detected on the TLC plate using autoradiography. Peaks corresponding to the parent tracer and radio-metabolites could be distinguished in the line profile through each sample (n = 8) in the autoradiographic image. Significant intersubject and intra-subject variability in radio-metabolites production could be observed with both tracers. For [18F]FEPPA, 50% of plasma activity was from radio-metabolites as early as 5-min post injection, while for [18F]FAZA, significant metabolites did not appear until 50-min post. Simulation study investigating the effect of radio-metabolite in the estimation of kinetic parameters indicated that 32–400% parameter error can result without radio-metabolites correction. Conclusion TLC coupled with autoradiography is a good alternative to high-performance liquid chromatography for radio-metabolite correction. The advantages of requiring only small blood samples (~ 100 μL) and of analyzing multiple samples simultaneously, make the method suitable for individual dynamic PET studies.

Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

2020 ◽  
Vol 33 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tatsushi Tanaka ◽  
Kohei Aoyama ◽  
Atsushi Suzuki ◽  
Shinji Saitoh ◽  
Haruo Mizuno
Keyword(s):  
Congenital Hypothyroidism ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Japanese Patients ◽  
Thyroid Stimulating Hormone ◽  
Allelic Variant ◽  
Genetic Investigation ◽  
Pathogenic Variants ◽  
Recessive Genes ◽  
Molecular Genetic Diagnosis

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

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