Objective:Perform a literary review of the interference in the results of biochemical laboratory tests caused by antihypertensive drugs.Methods:This is a review of the scientific literature with descriptive research p...Objective:Perform a literary review of the interference in the results of biochemical laboratory tests caused by antihypertensive drugs.Methods:This is a review of the scientific literature with descriptive research performed according to the PRISMA model using the databases PUBMED,SCIELO,MEDLINE,LILACS,and searches of Brazilian Ministry of Health and Federal Pharmacy Council publications,reagent kits and package inserts approved by ANVISA.Literature and papers in Portuguese and English were selected,prioritizing the years 2010 to 2020.Results:The diuretic class of antihypertensive drugs causes decreases glucose tolerance,thus resulting in an increase in triglycerides.In long-term use,the drug captopril can increase serum levels of potassium,creatine kinase and decreases blood sodium.Methyldopa causes an increase in AST levels.Propranolol is associated with an increase in triglyceride levels and a decrease in HDL and glucose levels.The constant use of losartan results in an increase in HDL,a decrease in uric acid levels and a slight and transient increase in transaminases.In the Gold Analisa,Bioclin and Labtest reagent kits,most of the alterations occur due to the increase in levels of serum biomarkers according to the class of the antihypertensive drug.Conclusions:Biochemical alterations in serum can result in false-positive or false-negative reports,since it can be observed that most of the dosages caused increases due to the physiological effect of the drugs.The antihypertensive drugs that showed the highest incidence of interference were captopril,atenolol,losartan and propranolol.展开更多
Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,...Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.展开更多
Organelle integrity and maintenance of protein homeostasis and purpose is essential for fundamental equilibrium and survivability.Autophagy is the primary process which regulates the distribution of different cell loa...Organelle integrity and maintenance of protein homeostasis and purpose is essential for fundamental equilibrium and survivability.Autophagy is the primary process which regulates the distribution of different cell loads to lysosomes for destruction and reuse.Extensive research illustrates the protective functions of autophagy against various diseases.Though in cancer,noticeably contrasting functions of autophagy have been evaluated in the prohibition of preliminary tumor evolution vs the continuance and,anabolic and catabolic variations of wellestablished and invasive tumors.Autophagy possesses numerous roles in tumor microenvironment(TME)establishment and associated immune cells function which is addressed in recent studies.Autophagic machinery which is employed in different autophagy-related pathways contributes to metastatic diseases and are distinct from classical autophagy.Therapeutic strategies based on the inhibition or induction of autophagy and related processes has helped in the designing of efficient anticancer drugs.According to the review,we evaluate and decipher the various purposes of autophagy and its association with autophagy mechanisms in course of tumor development,invasion and progression.We summarize the latest findings involving the role of these activities including tumor cells and TME and define further breakthrough in therapy aiming at autophagic activities in cancer.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)is a metabolic disorder causing hyperglycemia during pregnancy.Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progr...BACKGROUND Gestational diabetes mellitus(GDM)is a metabolic disorder causing hyperglycemia during pregnancy.Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progression of GDM.CD36 is a membrane glycoprotein involved in lipid metabolism and insulin sensitivity.Studies indicate that the CD36 gene is substantially linked to type 2 diabetes mellitus(T2DM)and could also influence GDM susceptibility.Insulin resistance and decreased insulin secretion are the hallmarks of T2DM,which is thought to have a similar genetic pathophysiology in GDM.AIM To investigate the impact of CD36 gene polymorphisms[rs1761667(G/A)and rs75326924(C/T)]and mRNA expression in GDM women.METHODS The case-control study involved a total of 400 pregnant women,(200 healthy controls and 200 GDM cases).The study of CD36 gene polymorphisms G/A(rs1761667)and C/T(rs75326924))were determined by polymerase chain reaction-restriction fragment length polymorphism.The mRNA expression study of CD36 gene was analyzed by quantitative polymerase chain reaction/quantitative real-time polymerase chain reaction followed by statistical analysis done using GraphPad Prism8 software(ver.8.0).RESULTS The study revealed statistically significant association(P<0.05)in anthropometric/biochemical parameters(age,gestational age,body mass index,fasting prandial glucose,post-prandial glucose,triglyceride,low-density lipoprotein)between GDM cases and healthy controls.CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms were significantly associated with GDM cases.The heterozygous genotypes(GA and CT)of both variants showed significant association(P=0.0001 and P=0.0025,odds ratio=2.683 and 2.022 respectively).Allele frequency of‘T’allele in CD36 C/T(rs75326924)polymorphism was also found to be significant(P=0.0046).CD36 gene was upregulated in individuals with GDM as compared to healthy controls(P=0.0001).However,the upregulation of gene expression was not significantly associated with the genotypes of CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms.CONCLUSION Heterozygous genotypes GA and CT of CD36 gene variants and expression are linked to GDM,potentially serving as predictive biomarkers for GDM susceptibility;further exploration needed in diverse ethnic communities.展开更多
Gestational diabetes mellitus(GDM)is a metabolic condition caused by chronic insulin resistance during pregnancy,affecting millions of women globally and causing significant health concerns.Its consequences are far-re...Gestational diabetes mellitus(GDM)is a metabolic condition caused by chronic insulin resistance during pregnancy,affecting millions of women globally and causing significant health concerns.Its consequences are far-reaching,associated with poor feto-maternal outcomes.GDM has serious implications on metabolic health in both mother and child.Early diagnosis and management of GDM are crucial to prevent related consequences.Traditional diagnostic and predictive biomarkers for GDM,including oral glucose tolerance test,adiponectin,resistin,etc.,have limitations.Recent advances in research have identified novel biomarkers for GDM,offering promising alternatives for early diagnosis and prediction to prevent the associated adverse pediatric outcomes.Emerging biomarkers include microRNAs,cell-free DNA,exosomes,glycolytic intermediates,inflammatory biomarkers(C-reactive protein and interleukin-6),metabolic biomarkers(Betatrophin,fetuin-A,etc.),etc.Emerging bidirectional communication pathway(gut microbiota gut-brain-axis)plays a crucial role in GDM pathophysiology,and could be a promising biomarker.Emerging technologies such as next-generation seque-ncing,metabolomics,and proteomics have enabled the discovery of novel bio-markers for GDM and related pediatric outcomes.This review aims to summarize the current state of knowledge on emerging biomarkers for GDM,including their diagnostic accuracy,predictive value,and potential clinical applications to improve feto-maternal outcomes by personalized medicine approaches.展开更多
Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a...Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.展开更多
Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a project...Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.展开更多
AIM： To undertake analysis of hepatitis A viral load, alanine aminotransferase （ALT）, and viral genotypes with duration of viremia, and to correlate these parameters with CD4^＋/ CD8^＋ lymphocyte populations that ...AIM： To undertake analysis of hepatitis A viral load, alanine aminotransferase （ALT）, and viral genotypes with duration of viremia, and to correlate these parameters with CD4^＋/ CD8^＋ lymphocyte populations that control cell-mediated immunity. METHODS： Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus （HAV） RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS： Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis （s-AH） and the remainder had a self-limited acute hepatitis A （AHA）, with one patient with fulminant disease （encephalopathy Grade IV） dying on the 4^th d. The ALT level was significantly higher both in AHA （1070.9±894.3; P = 0.0014） and s-AH （1713.9±886.3; P = 0.001） compared to normal controls （23.6±7.2）. The prothrombin time in s-AH patients （21.0 ±2.0; P=0.02） was significantly higher than in AHA （14.3±1.1;P = 0.44）. The CD4^＋/CD8^＋ ratio in AHA patients （1.17 ＋ 0.11; P = 0.22） and s-AH （0.83 ＋ 0.12; P = 0.0002） were lower than seen in normal healthy controls （1.52）. Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15TM or 30^th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and AIT values collected during the entire course of the selflimited infection were directly correlated but this was not the case for s-AH patients.CONCLUSION： Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.展开更多
AIM： To assess the significance of chromosome translo- cation t（11;18）（q21;q21）, B-cell lymphoma 10 （BCL-10） protein and He/icobacter py/ori （H. py/on） infection in gastric mucosa-associated lymphoid tissue ...AIM： To assess the significance of chromosome translo- cation t（11;18）（q21;q21）, B-cell lymphoma 10 （BCL-10） protein and He/icobacter py/ori （H. py/on） infection in gastric mucosa-associated lymphoid tissue （MALT） lymphoma in Colombia.展开更多
Glioblastoma(GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative...Glioblastoma(GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative in intent. Since the majority of altered signaling cascades involved in cancer establishment and progression eventually affect cell cycle progression, an alternative approach for cancer therapy is to develop innovative compounds that block the activity of crucial molecules needed by tumor cells to complete cell division. In this context, we review promising ongoing and future strategies for GBM therapeutics aimed towards G2/M inhibition such as anti-microtubule agents and targeted therapy against G2/M regulators like cyclin-dependent kinases,Aurora inhibitors, PLK1, BUB, 1, and BUBR1, and survivin. Moreover, we also include investigational agents in the preclinical and early clinical settings. Although several drugs were shown to be gliotoxic, most of them have not yet entered therapeutic trials. The use of either single exposure or a combination with novel compounds may lead to treatment alternatives for GBM patients in the near future.展开更多
Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,result...Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.展开更多
Chromosomal abnormalities are one of the major causes of male infertility. But the exact mechanism by which chromosomal anomalies induces infertility is still not clear. Many studies have documented the chromosomal ab...Chromosomal abnormalities are one of the major causes of male infertility. But the exact mechanism by which chromosomal anomalies induces infertility is still not clear. Many studies have documented the chromosomal abnormalities ranging from 2.2% to 15.7% in infertile men. The present study has been carried out to document and find out the genetic cause of male infertility in the Southern region of India. The cytogenetic analysis of 200 male infertile cases, referred due to primary infertility from 2009 to 2012, were analyzed by GTG banding and evaluated retrospectively. The semen analysis was also performed. A total of 15 cases (7.5%) showed chromosomal aberrations. Four (2%) were 47, XXY and mosaic 47,XXY;Two (1%) were structural autosomal abnormalities;Two (1%) were inversion Y;Seven (3.5%) cases were Y heterochromatin variants and 185 cases (92.5%) showed normal 46,XY karyotype. The chromosomal abnormalities in our study is also in agreement with the data from the literature. Also abnormal spermatogenesis is observed in these cases. Apart from chromosomal analysis further in depth molecular analysis and genetic counseling is suggestive in such cases, especially those interested in IVF technologies.展开更多
Fish scale wastes are generally discarded in the environment through fish processing industries and local market vendors. It is one of the excellent and efficient renewable bioproducts. Consequently, a number of bioac...Fish scale wastes are generally discarded in the environment through fish processing industries and local market vendors. It is one of the excellent and efficient renewable bioproducts. Consequently, a number of bioactive compounds have been identified including bioactive peptides, collagen, chitosan, and gelatin which are commercially marketed. The current study involves the extraction and generation of chitosan nanoparticles from fish scales. The synthesized chitosan nanosubstances were categorized by Field Emission Scanning Electron Microscopy (FESEM). The viability of utilizing fish scales as an economical bio-adsorbent for elimination of textile dye was studied on industrial effluent. Fourier transform infrared spectroscopy (FTIR) was used to study the dye adsorption of chitosan nanoparticles before and after the dye treatment. With chitosan nanoparticle treatment of the textile effluents, removal of COD was improved to 80% and the turbidity removal efficiency was improved up to 90%. Thus, the present study provides an excellent bio-adsorbent chitosan nanoparticle generated from fish scales which have potential application as an adsorbent in bioremediation like wastewater treatment.展开更多
After Alzheimer’s disease,Parkinson’s disease(PD)is the most common neurodegenerative disease.According to WHO data,about 1%of the world’s population over 60 years of age is affected by PD,and its incidence increas...After Alzheimer’s disease,Parkinson’s disease(PD)is the most common neurodegenerative disease.According to WHO data,about 1%of the world’s population over 60 years of age is affected by PD,and its incidence increases with age.Information about mortality plays a relevant role in the planning and distribution of financial resources in the areas of public health,social assistance and the like.Thus,this article aims to describe the evolution of PD mortality in the Brazilian state capitals,in the period from 2010 to 2019.A descriptive and retrospective study was conducted,based on data collection(number of deaths and estimated resident population),by sex and age group,available in the DATASUS SIM.Mortality rates were calculated per 100 thousand inhabitants;and statistical tests of linear regression,the t-test,ANOVA and the Tukey test,using the R program,were performed to evaluate the significance of the data.The number of deaths and mortality rates were higher in males compared to females and the incidence of mortality was higher in the over 80s.Notably,the southeastern region presented the highest mortality rates,which is to be expected because it concentrates the highest proportion of elderly people.It is hoped that such data will aid the implementation of public health policies and adequate social assistance for those affected by PD,in order to improve their quality of life.展开更多
AIM To investigate if mutations in TCF7 L2 are associated with "atypical diabetes" in the Uruguayan population.METHODS Healthy, nondiabetic controls(n = 133) and patients with type 2 diabetes(n = 177) were s...AIM To investigate if mutations in TCF7 L2 are associated with "atypical diabetes" in the Uruguayan population.METHODS Healthy, nondiabetic controls(n = 133) and patients with type 2 diabetes(n = 177) were selected from among the presenting population at level-3 referral healthcare centers in Uruguay. Patients with type 2 diabetes were subgrouped according to "atypical diabetes"(n = 92) and "classical diabetes"(n = 85). Genotyping for the rs12255372 and rs7903146 single nucleotide polymorphisms(SNPs) in the TCFTL2 gene was carried out with Taq Man? probes. Random samples were sequenced by Macrogen Ltd.(South Korea). Statistical analysis of the SNP data was carried out with the SNPStats online tool(http://bioinfo.iconcologia.net/SNPstats). The best inheritance model was chosen according to the lowest values of Akaike's information criterion and Bayesian information criterion. Differences between groups were determined by unpaired t-tests after checking the normal distribution or were converted to normalize the data. The association of SNPs was tested for matched case-control samples by using χ2 analysis and calculation of odds ratios(ORs) with 95% confidence intervals(CIs). All statistical tests were performed using SPSS v10.0 and EpiI nfo7 statistical packages. Significant statistical differences were assumed in all cases showing adjusted P < 0.05.RESULTS We genotyped two TCF7 L2 SNPs(rs7903146 and rs12255372) in a population-based sample of 310 Uruguayan subjects, including 133 healthy control subjects and 177 clinical diagnosed with type 2 diabetes. For both SNPs analyzed, the best model was the dominant type: rs12255372 = G/G vs G/T+T/T, OR = 0.63, 95%CI: 0.40-0.98, P < 0.05 and rs7903146 = C/C vs C/T+T/T, OR = 0.79, 95%CI: 0.41-1.55, P = 0.3. The rs12255372 SNP showed high association with the type 2 diabetes cases(OR = 1.60, 95%CI: 1.20-2.51, P < 0.05). However, when the type 2 diabetics group was analyzed according to the atypical and classical subgroupings, the association with diabetes existed only for rs12255372 and the classical subgroup(vs controls: OR = 2.1, 95%CI: 1.21-3.75, P < 0.05); no significant differences were found for either SNP or atypical diabetes.CONCLUSION This is the first time SNPs_TCF7 L2 were genotyped in a diabetic population stratified by genotype instead of phenotype. Classical and atypical patients showed statistical differences.展开更多
Chromosomal alterations can cause a number of diseases;therefore,early detection of these alterations is fundamental in the prevention and treatment of various abnormalities.In this sense,the objective of this study w...Chromosomal alterations can cause a number of diseases;therefore,early detection of these alterations is fundamental in the prevention and treatment of various abnormalities.In this sense,the objective of this study was to perform cytogenetic analysis of patients with phenotypic characteristics not yet clarified in order to determine the frequency of chromosomal alterations in patients treated in the public health system in Manaus,Brazil.A total of 98 patients with clinical suspicion of genetic syndrome were referred to the public health system in Manaus,Amazonas state.Genetic analyses were performed from lymphocyte culture and subsequent G-banding.Patient data were obtained through referral files and chromosomal a Analyses.Of the 98 karyotypes analyzed,65(66.3%)presented normal karyotype,18(18.4%)presented chromosomal alterations and 15(15.3%)were inconclusive.Of the alterations found,11(61.1%)corresponded to alterations of the numerical type and 7(38.9%)of the structural type.Of the chromosomal alterations identified,the one with the highest frequency was aneuploidy,which was significantly represented by 9 patients with Down’s syndrome,and different karyotypic mechanisms related to this syndrome were observed.There was also one case of deletion,one case of pericentric inversion,and two involving the sex chromosomes.The etiological confirmation of congenital anomalies is extremely important for the patient’s prognosis,and it is necessary to invest in cytomolecular tests,such as FISH and microarray in order to increase the rate of diagnosis.展开更多
BACKGROUND KBG syndrome is likely underdiagnosed because of mild and non-specific features in some affected patients especially before the upper permanent central incisors eruption at about the age of 7-8 years.Somati...BACKGROUND KBG syndrome is likely underdiagnosed because of mild and non-specific features in some affected patients especially before the upper permanent central incisors eruption at about the age of 7-8 years.Somatic mosaicisms are usually recognized in the parents only after a typically affected son is diagnosed with KBG syndrome.We describe for the first time the mosaicism of a novel variant in a child with a mild KBG phenotype.CASE SUMMARY Our patient presented at 24 mo of age with short stature,hand abnormalities,facial dysmorphism and mild developmental delay.Pituitary hypoplasia and central hypothyroidism were also detected.By next generation sequencing(NGS)analysis we found a novel deletion in the ANKRD11 gene(c.4880_4893del.),that can be classified as likely pathogenic for the syndrome,with the percentage of mutated allele of 36%.We considered this finding as causative of the mild and non-specific phenotype for KBG syndrome in our patient,as previously reported in adults.A heterozygous variant in HESX1 gene,classified as variant of uncertain significance,but suspected of causing pituitary hypoplasia and hormonal deficiency,was also found.The patient started levothyroxine and growth hormone treatment.CONCLUSION The increased use of NGS analysis may expand the phenotypic spectrum of KBG syndrome because it allows genetic diagnosis of somatic mosaicisms also in children.展开更多
Etiopathology of male infertility is highly complex and chromosome rearrangements play an important role in non-obstructive azoospermia (NOA). Testes is the unique organ, where, spermatogenesis regulates the prolifera...Etiopathology of male infertility is highly complex and chromosome rearrangements play an important role in non-obstructive azoospermia (NOA). Testes is the unique organ, where, spermatogenesis regulates the proliferation of germ cells and non-germinal cells (Sertoli cells & Leydig cells) work together in a synchronized fashion. Infertility is a genetic phenomenon and a variety of structural and numerical chromosome aberrations are well known to interfere with male infertility. The role of SycpT657C gene polymorphism has been poorly documented in the Indian population with special reference to non-obstructive azoospermic (NOA) cases. The present study has been designed with the aim to evaluate the following: 1) Cytogenetics study for evaluating the frequency of both structural and numerical chromosome variations in (NOA) cases by short-term peripheral blood lymphocyte (PBL) cultures;2) Genetic heterogenicity of the Sycp3 gene polymorphism by evaluating the frequency of T/C alleles. PCR-based analysis was carried out to characterize bands on agarose gel after ethidium bromide staining and bands were visualized on Gel-Doc system. Karyotype showing two new loci involving chromatid breaks 46,XY2q34, and 46,XY4q32 with the loss of DNA fragment of > 8.0 Mbp. Difference in the frequency of Robertsonian translocation (20%) and mosaicism (46,XY/47,XYY) were observed in the same karyotype. SYCP3 polymorphism shows significant changes in the frequency of TT genotype (43.33%) in homozygous conditions (wild type) and the calculated value of odd ratio (0.23) with a confidence interval varying from 0.08 - 0.71, suggesting an increased risk of developing infertility. To enhance the power of significance, two genotypes were combined together CC + TC which again showed significance with respect to controls. Data of the present study concludes that genetic heterogenicity of Sycp3 gene polymorphism and chromosomal aberrations with loss of DNA (8 Mbp) together confirm of developing risk of infertility in the NOA population.展开更多
Background:There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease(ADPKD)and connective tissue disorders.A simultaneous occurrence of osteogenesis imperfecta(OI)type ...Background:There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease(ADPKD)and connective tissue disorders.A simultaneous occurrence of osteogenesis imperfecta(OI)type I and ADPKD has not been observed so far.Methods:This report presents the first patient with OI type I and ADPKD.Results:Mutational analysis of PKD1 and COL1A1 in the index patient revealed a heterozygous mutation in each of the two genes.Mutational analysis of the parents indicated the mother as a carrier of the PKD1 mutation and the father as a carrier of the COL1A1 mutation.The simultaneous occurrence of both disorders has an estimated frequency of 3.5:100000000.Conclusion:In singular cases,ADPKD can occur in combination with other rare disorders,e.g.connective tissue disorders.展开更多
文摘Objective:Perform a literary review of the interference in the results of biochemical laboratory tests caused by antihypertensive drugs.Methods:This is a review of the scientific literature with descriptive research performed according to the PRISMA model using the databases PUBMED,SCIELO,MEDLINE,LILACS,and searches of Brazilian Ministry of Health and Federal Pharmacy Council publications,reagent kits and package inserts approved by ANVISA.Literature and papers in Portuguese and English were selected,prioritizing the years 2010 to 2020.Results:The diuretic class of antihypertensive drugs causes decreases glucose tolerance,thus resulting in an increase in triglycerides.In long-term use,the drug captopril can increase serum levels of potassium,creatine kinase and decreases blood sodium.Methyldopa causes an increase in AST levels.Propranolol is associated with an increase in triglyceride levels and a decrease in HDL and glucose levels.The constant use of losartan results in an increase in HDL,a decrease in uric acid levels and a slight and transient increase in transaminases.In the Gold Analisa,Bioclin and Labtest reagent kits,most of the alterations occur due to the increase in levels of serum biomarkers according to the class of the antihypertensive drug.Conclusions:Biochemical alterations in serum can result in false-positive or false-negative reports,since it can be observed that most of the dosages caused increases due to the physiological effect of the drugs.The antihypertensive drugs that showed the highest incidence of interference were captopril,atenolol,losartan and propranolol.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,and Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022).
文摘Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.
基金Supported by DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level Ⅱ),No.TG BT/INF/22/SP47623/2022.
文摘Organelle integrity and maintenance of protein homeostasis and purpose is essential for fundamental equilibrium and survivability.Autophagy is the primary process which regulates the distribution of different cell loads to lysosomes for destruction and reuse.Extensive research illustrates the protective functions of autophagy against various diseases.Though in cancer,noticeably contrasting functions of autophagy have been evaluated in the prohibition of preliminary tumor evolution vs the continuance and,anabolic and catabolic variations of wellestablished and invasive tumors.Autophagy possesses numerous roles in tumor microenvironment(TME)establishment and associated immune cells function which is addressed in recent studies.Autophagic machinery which is employed in different autophagy-related pathways contributes to metastatic diseases and are distinct from classical autophagy.Therapeutic strategies based on the inhibition or induction of autophagy and related processes has helped in the designing of efficient anticancer drugs.According to the review,we evaluate and decipher the various purposes of autophagy and its association with autophagy mechanisms in course of tumor development,invasion and progression.We summarize the latest findings involving the role of these activities including tumor cells and TME and define further breakthrough in therapy aiming at autophagic activities in cancer.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022)Department of Science and Technology-SERB Power Grant Scheme,No.SPG/2021/00545.
文摘BACKGROUND Gestational diabetes mellitus(GDM)is a metabolic disorder causing hyperglycemia during pregnancy.Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progression of GDM.CD36 is a membrane glycoprotein involved in lipid metabolism and insulin sensitivity.Studies indicate that the CD36 gene is substantially linked to type 2 diabetes mellitus(T2DM)and could also influence GDM susceptibility.Insulin resistance and decreased insulin secretion are the hallmarks of T2DM,which is thought to have a similar genetic pathophysiology in GDM.AIM To investigate the impact of CD36 gene polymorphisms[rs1761667(G/A)and rs75326924(C/T)]and mRNA expression in GDM women.METHODS The case-control study involved a total of 400 pregnant women,(200 healthy controls and 200 GDM cases).The study of CD36 gene polymorphisms G/A(rs1761667)and C/T(rs75326924))were determined by polymerase chain reaction-restriction fragment length polymorphism.The mRNA expression study of CD36 gene was analyzed by quantitative polymerase chain reaction/quantitative real-time polymerase chain reaction followed by statistical analysis done using GraphPad Prism8 software(ver.8.0).RESULTS The study revealed statistically significant association(P<0.05)in anthropometric/biochemical parameters(age,gestational age,body mass index,fasting prandial glucose,post-prandial glucose,triglyceride,low-density lipoprotein)between GDM cases and healthy controls.CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms were significantly associated with GDM cases.The heterozygous genotypes(GA and CT)of both variants showed significant association(P=0.0001 and P=0.0025,odds ratio=2.683 and 2.022 respectively).Allele frequency of‘T’allele in CD36 C/T(rs75326924)polymorphism was also found to be significant(P=0.0046).CD36 gene was upregulated in individuals with GDM as compared to healthy controls(P=0.0001).However,the upregulation of gene expression was not significantly associated with the genotypes of CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms.CONCLUSION Heterozygous genotypes GA and CT of CD36 gene variants and expression are linked to GDM,potentially serving as predictive biomarkers for GDM susceptibility;further exploration needed in diverse ethnic communities.
基金Supported by DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level Ⅱ),No.TG BT/INF/22/SP47623/2022Maulana Azad National Fellowship,University Grants Commission,New Delhi,Department of Biotechnology,New Delhi,No.F.82-27/2019(SA Ⅲ).
文摘Gestational diabetes mellitus(GDM)is a metabolic condition caused by chronic insulin resistance during pregnancy,affecting millions of women globally and causing significant health concerns.Its consequences are far-reaching,associated with poor feto-maternal outcomes.GDM has serious implications on metabolic health in both mother and child.Early diagnosis and management of GDM are crucial to prevent related consequences.Traditional diagnostic and predictive biomarkers for GDM,including oral glucose tolerance test,adiponectin,resistin,etc.,have limitations.Recent advances in research have identified novel biomarkers for GDM,offering promising alternatives for early diagnosis and prediction to prevent the associated adverse pediatric outcomes.Emerging biomarkers include microRNAs,cell-free DNA,exosomes,glycolytic intermediates,inflammatory biomarkers(C-reactive protein and interleukin-6),metabolic biomarkers(Betatrophin,fetuin-A,etc.),etc.Emerging bidirectional communication pathway(gut microbiota gut-brain-axis)plays a crucial role in GDM pathophysiology,and could be a promising biomarker.Emerging technologies such as next-generation seque-ncing,metabolomics,and proteomics have enabled the discovery of novel bio-markers for GDM and related pediatric outcomes.This review aims to summarize the current state of knowledge on emerging biomarkers for GDM,including their diagnostic accuracy,predictive value,and potential clinical applications to improve feto-maternal outcomes by personalized medicine approaches.
基金Supported by Agencies viz Department of Biotechnology(DBT),Indian Council of Medical Research(ICMR),Department of Science and Technology(DST)and Centre of Excellence(COE),UP Government,India for generous grants to our laboratory for diabetes research
文摘Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.
文摘Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.
文摘AIM： To undertake analysis of hepatitis A viral load, alanine aminotransferase （ALT）, and viral genotypes with duration of viremia, and to correlate these parameters with CD4^＋/ CD8^＋ lymphocyte populations that control cell-mediated immunity. METHODS： Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus （HAV） RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS： Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis （s-AH） and the remainder had a self-limited acute hepatitis A （AHA）, with one patient with fulminant disease （encephalopathy Grade IV） dying on the 4^th d. The ALT level was significantly higher both in AHA （1070.9±894.3; P = 0.0014） and s-AH （1713.9±886.3; P = 0.001） compared to normal controls （23.6±7.2）. The prothrombin time in s-AH patients （21.0 ±2.0; P=0.02） was significantly higher than in AHA （14.3±1.1;P = 0.44）. The CD4^＋/CD8^＋ ratio in AHA patients （1.17 ＋ 0.11; P = 0.22） and s-AH （0.83 ＋ 0.12; P = 0.0002） were lower than seen in normal healthy controls （1.52）. Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15TM or 30^th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and AIT values collected during the entire course of the selflimited infection were directly correlated but this was not the case for s-AH patients.CONCLUSION： Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.
基金Supported by A grant from Universidad Nacional de Colombia
文摘AIM： To assess the significance of chromosome translo- cation t（11;18）（q21;q21）, B-cell lymphoma 10 （BCL-10） protein and He/icobacter py/ori （H. py/on） infection in gastric mucosa-associated lymphoid tissue （MALT） lymphoma in Colombia.
基金supported by The Sao Paulo Research Foundation–FAPESP(Grant No.12/16888-8 and 2009/50118-2)
文摘Glioblastoma(GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative in intent. Since the majority of altered signaling cascades involved in cancer establishment and progression eventually affect cell cycle progression, an alternative approach for cancer therapy is to develop innovative compounds that block the activity of crucial molecules needed by tumor cells to complete cell division. In this context, we review promising ongoing and future strategies for GBM therapeutics aimed towards G2/M inhibition such as anti-microtubule agents and targeted therapy against G2/M regulators like cyclin-dependent kinases,Aurora inhibitors, PLK1, BUB, 1, and BUBR1, and survivin. Moreover, we also include investigational agents in the preclinical and early clinical settings. Although several drugs were shown to be gliotoxic, most of them have not yet entered therapeutic trials. The use of either single exposure or a combination with novel compounds may lead to treatment alternatives for GBM patients in the near future.
文摘Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.
文摘Chromosomal abnormalities are one of the major causes of male infertility. But the exact mechanism by which chromosomal anomalies induces infertility is still not clear. Many studies have documented the chromosomal abnormalities ranging from 2.2% to 15.7% in infertile men. The present study has been carried out to document and find out the genetic cause of male infertility in the Southern region of India. The cytogenetic analysis of 200 male infertile cases, referred due to primary infertility from 2009 to 2012, were analyzed by GTG banding and evaluated retrospectively. The semen analysis was also performed. A total of 15 cases (7.5%) showed chromosomal aberrations. Four (2%) were 47, XXY and mosaic 47,XXY;Two (1%) were structural autosomal abnormalities;Two (1%) were inversion Y;Seven (3.5%) cases were Y heterochromatin variants and 185 cases (92.5%) showed normal 46,XY karyotype. The chromosomal abnormalities in our study is also in agreement with the data from the literature. Also abnormal spermatogenesis is observed in these cases. Apart from chromosomal analysis further in depth molecular analysis and genetic counseling is suggestive in such cases, especially those interested in IVF technologies.
文摘Fish scale wastes are generally discarded in the environment through fish processing industries and local market vendors. It is one of the excellent and efficient renewable bioproducts. Consequently, a number of bioactive compounds have been identified including bioactive peptides, collagen, chitosan, and gelatin which are commercially marketed. The current study involves the extraction and generation of chitosan nanoparticles from fish scales. The synthesized chitosan nanosubstances were categorized by Field Emission Scanning Electron Microscopy (FESEM). The viability of utilizing fish scales as an economical bio-adsorbent for elimination of textile dye was studied on industrial effluent. Fourier transform infrared spectroscopy (FTIR) was used to study the dye adsorption of chitosan nanoparticles before and after the dye treatment. With chitosan nanoparticle treatment of the textile effluents, removal of COD was improved to 80% and the turbidity removal efficiency was improved up to 90%. Thus, the present study provides an excellent bio-adsorbent chitosan nanoparticle generated from fish scales which have potential application as an adsorbent in bioremediation like wastewater treatment.
文摘After Alzheimer’s disease,Parkinson’s disease(PD)is the most common neurodegenerative disease.According to WHO data,about 1%of the world’s population over 60 years of age is affected by PD,and its incidence increases with age.Information about mortality plays a relevant role in the planning and distribution of financial resources in the areas of public health,social assistance and the like.Thus,this article aims to describe the evolution of PD mortality in the Brazilian state capitals,in the period from 2010 to 2019.A descriptive and retrospective study was conducted,based on data collection(number of deaths and estimated resident population),by sex and age group,available in the DATASUS SIM.Mortality rates were calculated per 100 thousand inhabitants;and statistical tests of linear regression,the t-test,ANOVA and the Tukey test,using the R program,were performed to evaluate the significance of the data.The number of deaths and mortality rates were higher in males compared to females and the incidence of mortality was higher in the over 80s.Notably,the southeastern region presented the highest mortality rates,which is to be expected because it concentrates the highest proportion of elderly people.It is hoped that such data will aid the implementation of public health policies and adequate social assistance for those affected by PD,in order to improve their quality of life.
文摘AIM To investigate if mutations in TCF7 L2 are associated with "atypical diabetes" in the Uruguayan population.METHODS Healthy, nondiabetic controls(n = 133) and patients with type 2 diabetes(n = 177) were selected from among the presenting population at level-3 referral healthcare centers in Uruguay. Patients with type 2 diabetes were subgrouped according to "atypical diabetes"(n = 92) and "classical diabetes"(n = 85). Genotyping for the rs12255372 and rs7903146 single nucleotide polymorphisms(SNPs) in the TCFTL2 gene was carried out with Taq Man? probes. Random samples were sequenced by Macrogen Ltd.(South Korea). Statistical analysis of the SNP data was carried out with the SNPStats online tool(http://bioinfo.iconcologia.net/SNPstats). The best inheritance model was chosen according to the lowest values of Akaike's information criterion and Bayesian information criterion. Differences between groups were determined by unpaired t-tests after checking the normal distribution or were converted to normalize the data. The association of SNPs was tested for matched case-control samples by using χ2 analysis and calculation of odds ratios(ORs) with 95% confidence intervals(CIs). All statistical tests were performed using SPSS v10.0 and EpiI nfo7 statistical packages. Significant statistical differences were assumed in all cases showing adjusted P < 0.05.RESULTS We genotyped two TCF7 L2 SNPs(rs7903146 and rs12255372) in a population-based sample of 310 Uruguayan subjects, including 133 healthy control subjects and 177 clinical diagnosed with type 2 diabetes. For both SNPs analyzed, the best model was the dominant type: rs12255372 = G/G vs G/T+T/T, OR = 0.63, 95%CI: 0.40-0.98, P < 0.05 and rs7903146 = C/C vs C/T+T/T, OR = 0.79, 95%CI: 0.41-1.55, P = 0.3. The rs12255372 SNP showed high association with the type 2 diabetes cases(OR = 1.60, 95%CI: 1.20-2.51, P < 0.05). However, when the type 2 diabetics group was analyzed according to the atypical and classical subgroupings, the association with diabetes existed only for rs12255372 and the classical subgroup(vs controls: OR = 2.1, 95%CI: 1.21-3.75, P < 0.05); no significant differences were found for either SNP or atypical diabetes.CONCLUSION This is the first time SNPs_TCF7 L2 were genotyped in a diabetic population stratified by genotype instead of phenotype. Classical and atypical patients showed statistical differences.
文摘Chromosomal alterations can cause a number of diseases;therefore,early detection of these alterations is fundamental in the prevention and treatment of various abnormalities.In this sense,the objective of this study was to perform cytogenetic analysis of patients with phenotypic characteristics not yet clarified in order to determine the frequency of chromosomal alterations in patients treated in the public health system in Manaus,Brazil.A total of 98 patients with clinical suspicion of genetic syndrome were referred to the public health system in Manaus,Amazonas state.Genetic analyses were performed from lymphocyte culture and subsequent G-banding.Patient data were obtained through referral files and chromosomal a Analyses.Of the 98 karyotypes analyzed,65(66.3%)presented normal karyotype,18(18.4%)presented chromosomal alterations and 15(15.3%)were inconclusive.Of the alterations found,11(61.1%)corresponded to alterations of the numerical type and 7(38.9%)of the structural type.Of the chromosomal alterations identified,the one with the highest frequency was aneuploidy,which was significantly represented by 9 patients with Down’s syndrome,and different karyotypic mechanisms related to this syndrome were observed.There was also one case of deletion,one case of pericentric inversion,and two involving the sex chromosomes.The etiological confirmation of congenital anomalies is extremely important for the patient’s prognosis,and it is necessary to invest in cytomolecular tests,such as FISH and microarray in order to increase the rate of diagnosis.
文摘BACKGROUND KBG syndrome is likely underdiagnosed because of mild and non-specific features in some affected patients especially before the upper permanent central incisors eruption at about the age of 7-8 years.Somatic mosaicisms are usually recognized in the parents only after a typically affected son is diagnosed with KBG syndrome.We describe for the first time the mosaicism of a novel variant in a child with a mild KBG phenotype.CASE SUMMARY Our patient presented at 24 mo of age with short stature,hand abnormalities,facial dysmorphism and mild developmental delay.Pituitary hypoplasia and central hypothyroidism were also detected.By next generation sequencing(NGS)analysis we found a novel deletion in the ANKRD11 gene(c.4880_4893del.),that can be classified as likely pathogenic for the syndrome,with the percentage of mutated allele of 36%.We considered this finding as causative of the mild and non-specific phenotype for KBG syndrome in our patient,as previously reported in adults.A heterozygous variant in HESX1 gene,classified as variant of uncertain significance,but suspected of causing pituitary hypoplasia and hormonal deficiency,was also found.The patient started levothyroxine and growth hormone treatment.CONCLUSION The increased use of NGS analysis may expand the phenotypic spectrum of KBG syndrome because it allows genetic diagnosis of somatic mosaicisms also in children.
文摘Etiopathology of male infertility is highly complex and chromosome rearrangements play an important role in non-obstructive azoospermia (NOA). Testes is the unique organ, where, spermatogenesis regulates the proliferation of germ cells and non-germinal cells (Sertoli cells & Leydig cells) work together in a synchronized fashion. Infertility is a genetic phenomenon and a variety of structural and numerical chromosome aberrations are well known to interfere with male infertility. The role of SycpT657C gene polymorphism has been poorly documented in the Indian population with special reference to non-obstructive azoospermic (NOA) cases. The present study has been designed with the aim to evaluate the following: 1) Cytogenetics study for evaluating the frequency of both structural and numerical chromosome variations in (NOA) cases by short-term peripheral blood lymphocyte (PBL) cultures;2) Genetic heterogenicity of the Sycp3 gene polymorphism by evaluating the frequency of T/C alleles. PCR-based analysis was carried out to characterize bands on agarose gel after ethidium bromide staining and bands were visualized on Gel-Doc system. Karyotype showing two new loci involving chromatid breaks 46,XY2q34, and 46,XY4q32 with the loss of DNA fragment of > 8.0 Mbp. Difference in the frequency of Robertsonian translocation (20%) and mosaicism (46,XY/47,XYY) were observed in the same karyotype. SYCP3 polymorphism shows significant changes in the frequency of TT genotype (43.33%) in homozygous conditions (wild type) and the calculated value of odd ratio (0.23) with a confidence interval varying from 0.08 - 0.71, suggesting an increased risk of developing infertility. To enhance the power of significance, two genotypes were combined together CC + TC which again showed significance with respect to controls. Data of the present study concludes that genetic heterogenicity of Sycp3 gene polymorphism and chromosomal aberrations with loss of DNA (8 Mbp) together confirm of developing risk of infertility in the NOA population.
文摘Background:There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease(ADPKD)and connective tissue disorders.A simultaneous occurrence of osteogenesis imperfecta(OI)type I and ADPKD has not been observed so far.Methods:This report presents the first patient with OI type I and ADPKD.Results:Mutational analysis of PKD1 and COL1A1 in the index patient revealed a heterozygous mutation in each of the two genes.Mutational analysis of the parents indicated the mother as a carrier of the PKD1 mutation and the father as a carrier of the COL1A1 mutation.The simultaneous occurrence of both disorders has an estimated frequency of 3.5:100000000.Conclusion:In singular cases,ADPKD can occur in combination with other rare disorders,e.g.connective tissue disorders.
