Genetic Variability of the Paired Box Transcription Factor; PAX8 Gene: Guidance Towards Treatment Strategies in a Cohort of Congenital Hypothyroidism

2021 ◽  
Author(s):  
Sohier S. Abou El-Ella ◽  
Essam Shawky A.E.H. Khattab ◽  
Rehab K. Beddah ◽  
Naglaa Fathy Barseem
Keyword(s):  
Genetic Variability ◽  
Congenital Hypothyroidism ◽  
Novel Mutation ◽  
Treatment Strategies ◽  
Group I ◽  
Egyptian Patients ◽  
Pax8 Gene ◽  
Healthy Control ◽  
And Function ◽  
Thyroid Development

AbstractThe contribution of PAX8 genetic variants to congenital hypothyroidism (CH) is not well understood. We aimed to study the genetic variability of exons 3 and 5 of PAX8 gene among a cohort of children with congenital hypothyroidism in correspondence to their clinical aspect. Blood samples were collected from 117 children (63 girls and 54 boys) with CH and enrolled as cases (Group I). All cases underwent biochemical confirmation with low FT4 and high TSH levels and thyroid gland imaging, along with equal number of matched apparently healthy individuals who served as controls (Group II). Genomic materials for exons 3 and 5 of PAX8 gene were extracted, amplified by PCR, detected by electrophoresis, purified, and sequenced by the Sanger technique through the application of ABI 3730x1 DNA Sequencer. Out of 117 cases, eight different effective PAX8 mutations were detected in exon 3 (G23D, V35I, I34T, Q40P, p.R31C, p.R31H, p.R31A, and p.I47T) in 14 patients with their sonographic findings ranged from normal, hypoplastic to thyroid agenesis. Besides the reported mutations, one novel mutation; R31A was detected in 1 euotopic case. Exon 5 analysis revealed no detected mutations elsewhere. In contrast, all healthy control children showed no mutation and normal sonographic findings. Mutations in exon 3 of PAX8 gene, implies its important role in thyroid development and function, as a first estimate of PA8 mutation rate in Egyptian patients with CH having normal and dysgenetic gland. Using ultrasound is mandatory for diagnosis and guiding the treatment of children with CH.

scholarly journals Whole Genome 5′-Methylcytosine Level Quantification in Cirrhotic HCV-Infected Egyptian Patients with and without Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ahmed M. Awad ◽  
Wafaa S. Ragab ◽  
Nourhan Degheidy ◽  
Said Ahmed Ooda
Keyword(s):  
Dna Methylation ◽  
Negative Correlation ◽  
Epigenetic Mechanism ◽  
Control Group ◽  
Whole Genome ◽  
Group I ◽  
Egyptian Patients ◽  
Healthy Control ◽  
Cirrhotic Patients ◽  
Group Ii

DNA methylation is an epigenetic mechanism used by cells to control gene expression. DNA methylation is a commonly used epigenetic signaling tool that can hold genes in the “off” position. Chronic infection with hepatitis C virus (HCV) is considered a major risk for chronic liver impairment. It is the most common leading cause of HCC. The present work is aimed at studying whole genome 5′-methylcytosine levels in cirrhotic HCV-infected Egyptian patients. In the present study, 120 Egyptian adults were included. They were divided into two groups: group І (40 apparently healthy control subjects) and group ІІ (80 HCV-infected patients). Furthermore, group II was subdivided into 2 subgroups according to the presence of HCC in HCV-infected subjects. To all studied subjects, the level of 5-mC% was measured in peripheral blood. In the present study, the median of 5′-methylcytosine% in the control group (group I) was 2.5, in the HCV group (group IIa) was 2.45, and in the HCC group (group II b) was 2.25. A stepwise decrease in 5′-methylcytosine% from the control (group I) toward HCC (group IIb) was observed, taking into consideration that the stepwise global hypomethylation was not statistically significant (p=0.811). There was a negative correlation between ALT and 5′-methylcytosine% (p=−0.029). From this study, we can conclude that global DNA 5′-methylcytosine% does not differ in HCV-infected cirrhotic patients and HCC patients when compared to normal controls. Consecutively, we had concluded that there is no impact of 5′-methylcytosine% on the development of liver cirrhosis or HCC. Moreover, the negative correlation between 5′-methylcytosine% and serum ALT level denotes a trend of decrease in 5′-methylcytosine% with more liver damage.

scholarly journals Characterization of a Novel Loss of Function Mutation of PAX8 in a Familial Case of Congenital Hypothyroidism with In-Place, Normal-Sized Thyroid

2004 ◽  
Vol 89 (9) ◽  
pp. 4285-4291 ◽  
Author(s):  
Laurent Meeus ◽  
Brigitte Gilbert ◽  
Catherine Rydlewski ◽  
Jasmine Parma ◽  
Anne Lienhardt Roussie ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Congenital Hypothyroidism ◽  
Novel Mutation ◽  
Gene Promoter ◽  
Loss Of Function ◽  
Thyroid Dysgenesis ◽  
Cis Element ◽  
Ability To Act ◽  
Pax8 Gene ◽  
Functional Analyses

Thyroid dysgenesis is the most common cause of congenital hypothyroidism, a relatively frequent disease affecting 1 in 3000–4000 newborns. Whereas most cases are sporadic, mutations in transcription factors implicated in thyroid development have been shown to cause a minority of cases transmitted as monogenic Mendelian diseases. PAX8 is one of these transcription factors, and so far, five mutations have been identified in its paired domain in patients with thyroid dysgenesis. We have identified a novel mutation of PAX8, in the heterozygous state, in a father and his two children both presenting with congenital hypothyroidism associated with an in-place thyroid of normal size at birth. In addition, one of the affected siblings displayed unilateral kidney agenesis. The mutation substitutes a highly conserved serine in position 54 of the DNA-binding domain of the protein (S54G mutation) by a glycine. Functional analyses of the mutant protein (PAX8-S54G) demonstrated that it is unable to bind a specific cis-element of the thyroperoxidase gene promoter in EMSAs and that it has almost completely lost the ability to act in synergy with Titf1 to transactivate transcription from the thyroglobulin promoter/enhancer. These results indicate that loss of function mutations of the PAX8 gene may cause congenital hypothyroidism in the absence of thyroid hypoplasia.

scholarly journals Mutations in the gene encoding paired box domain (PAX8) are not a frequent cause of congenital hypothyroidism (CH) in Iranian patients with thyroid dysgenesis

2010 ◽  
Vol 54 (6) ◽  
pp. 555-559 ◽  
Author(s):  
Frouzandeh Mahjoubi ◽  
Mona Malek Mohammadi ◽  
Maryam Montazeri ◽  
Masoud Aminii ◽  
Mahin Hashemipour
Keyword(s):  
Transcription Factor ◽  
Congenital Hypothyroidism ◽  
Single Strand Conformation Polymorphism ◽  
Clinical Tests ◽  
Gene Encoding ◽  
Thyroid Dysgenesis ◽  
Pax8 Gene ◽  
And Function ◽  
Conformation Polymorphism ◽  
Iranian Patients

OBJECTIVE: Congenital hypothyroidism (CH) may be caused by defects in the thyroid or in one of the stages in the synthesis of thyroid hormones. Thyroid dysgenesis may be associated with mutation in the paired box transcription factor 8 (PAX8) gene. We attempted to screen PAX8 gene mutation in 50 CH patients with thyroid dysgenesis. SUBJECTS AND METHODS: The patients were classified in two groups as agenesis and ectopic based on biochemical and para clinical tests. By employing PCR, Single Strand Conformation Polymorphism (SSCP) and sequencing, exons 3 to 12 of PAX8 gene with their exon-intron boundaries were studied. RESULTS: No mutation was found in these patients in any of the exons. CONCLUSION: Our results, once again, indicate that the PAX8 mutation rate is very low and can only explain a minority of the cases. Therefore, it is highly needed to further investigate the genes controlling development and function of thyroid.

scholarly journals A New Mutation in the Promoter Region of the PAX8 Gene Causes True Congenital Hypothyroidism with Thyroid Hypoplasia in a Girl with Down's Syndrome

Thyroid ◽  
2014 ◽  
Vol 24 (6) ◽  
pp. 939-944 ◽  
Author(s):  
Pia Hermanns ◽  
Scott Shepherd ◽  
Mohamed Mansor ◽  
John Schulga ◽  
Jez Jones ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Promoter Region ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
New Mutation ◽  
Pax8 Gene

scholarly journals The Effectiveness Of Quadriceps Strengthening Exercises Combined With Neuromuscular Electrical Stimulation on Patellofemoral Pain Syndrome

2017 ◽  
Vol 5 (2_suppl2) ◽  
pp. 2325967117S0010
Author(s):  
Sezen Karabörklü Argut ◽  
Nilgün Türker ◽  
Derya Çelik ◽  
Önder İsmet Kılıçoğlu
Keyword(s):  
Electrical Stimulation ◽  
Muscle Strength ◽  
Neuromuscular Electrical Stimulation ◽  
Pain Syndrome ◽  
Quadriceps Strength ◽  
Patellofemoral Pain ◽  
Group I ◽  
Strengthening Exercises ◽  
Group Ii ◽  
And Function

Objective: The weakness of the quadriceps strength in patellofemoral pain syndrome (PFPS) is very evident. Therefore, quadriceps strengthening exercises are very important part of the rehabilitation program. Neuromuscular Electrical Stimulation (NMES) is considered one of the methods for increasing quadriceps muscle strength. To evaluate the effectiveness of combined NMES and strengthening exercises to improve the recovery of quadriceps strength and function in patients with PFPS. Methods: This study was planned as a randomized controlled pilot study. A total of 27 patients (mean age=38.9±10.8 years, range=20-60 years; 16 females) with PFPS were assessed and randomly assigned into 2 groups. Group I received a standard program (quadriceps strengthening, hip strengthening and hamstring stretching) and NMES combined with quadriceps strengthening exercises simultaneously. Group II received the same standard program without NMES. Both groups were enrolled 3 times per week for 40 minutes per day in 6 weeks. Patients were assessed at the baseline, 3 rd, 6th, and 12th weeks of treatment. Quadriceps strength was evaluated by isokinetic dynamometer. The range of motion at testing was set between 0 for extension to 90 for flexion. The test was performed at 60 degrees/sn and concentric maximum peak torque value was recorded. Kujala and Lysholm scores were used for functional assessments. The data were analyzed using the SPSS 20.0. Shapiro-Wilk test was used to assess the distribution of data. The changes in dependent variables before treatment, 3 rd, 6th, and 12th weeks were analyzed using a 2 by 4 mixed-model analysis of variance (ANOVA). Pairwise comparisons with paired t test were used to determine whether the Group I or Group II, has changed over time. An intention- to- treat analysis was performed to impute values for missing data. An alpha level of 0.05 was established. Results: The study was completed with 20 patients. Group I (n=10; mean age=39.4±8.5 years; 7 females) and group II (n=10; mean age=43.2±11.7 years; 5 females) had no differences in pre-operative measures (p>.05). There was significant improvements in within groups statistics of all parameters for both groups (p<.05). No differences in quadriceps strength, Kujala and Lysholm scores between groups were found at the different time points (F= 0.86; p = 0.12, F=0,001; p =0.97, F=0.12; p=0.73, respectively) Conclusion: NMES combined with quadriceps strengthening exercises has no additional effect on PFPS patients’ on muscle strength and function. When considering these results, we believe that there is no need to continue the study in progress. [Table: see text]

scholarly journals Right Heart Structure, Geometry and Function Assessed by Echocardiography in 6-Year-Old Children Born Extremely Preterm—A Population-Based Cohort Study

2020 ◽  
Vol 10 (1) ◽  
pp. 122
Author(s):  
Lilly-Ann Mohlkert ◽  
Jenny Hallberg ◽  
Olof Broberg ◽  
Gunnar Sjöberg ◽  
Annika Rydberg ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Ductus Arteriosus ◽  
Population Based ◽  
Right Heart ◽  
Functional Changes ◽  
Cardiac Phenotype ◽  
Extremely Preterm ◽  
Healthy Control ◽  
The Right ◽  
And Function

Preterm birth has been associated with altered cardiac phenotype in adults. Our aim was to test the hypothesis that children surviving extremely preterm birth have important structural or functional changes of the right heart or pulmonary circulation. We also examined relations between birth size, gestational age, neonatal diagnoses of bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) with cardiac outcomes. We assessed a population-based cohort of children born in Sweden before 27 weeks of gestation with echocardiography at 6.5 years of age (n = 176). Each preterm child was matched to a healthy control child born at term. Children born preterm had significantly smaller right atria, right ventricles with smaller widths, higher relative wall thickness and higher estimated pulmonary vascular resistance (PVR) than controls. In preterm children, PVR and right ventricular myocardial performance index (RVmpi’) were significantly higher in those with a PDA as neonates than in those without PDA, but no such associations were found with BPD. In conclusion, children born extremely preterm exhibit higher estimated PVR, altered right heart structure and function compared with children born at term.

Impact of maternal thyroid disease on neonatal thyroid status

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Lakshmi Venugopalan ◽  
Aishwarya Rajan ◽  
Hemchand. K. Prasad ◽  
Anupama Sankaran ◽  
Gnanabalan Murugesan ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Thyroid Stimulating Hormone ◽  
Study Group ◽  
Thyroid Status ◽  
Case Identification ◽  
Group I ◽  
Group Ii ◽  
Maternal Thyroid ◽  
Heel Prick ◽  
Stimulating Hormone

AbstractObjectivesPrevalence of Maternal and congenital hypothyroidism is on the rise. To present the thyroid stimulating hormone screening results in babies born to hypothyroid mothers and assess the burden, aetiology of hypothyroidism in these babiesMethodsAll antenatal mothers attending our hospital during the study period were enrolled into the study. Group I includes 249 term babies born to hypothyroid mothers and group II comprises 2154 newborns born to mothers who are euthyroid. Heel prick thyroid stimulating hormone was done for all newborns on day 3 for both groups. Confirmatory venous testing was done for all for babies in group I and screen positives belonging to group II. Evaluation and therapy done as per standard guidelines.ResultsThyroid stimulating hormone values in the two groups are presented. There was significant correlation between peak maternal thyroid stimulating hormone and neonatal day 3 heel prick in group I (r=0.7, P<0.05). The prevalence of positive screening test in groups I and II was 3.8 and 1.03% (p<0.05) whereas corresponding values for confirmed disease was 4.3 and 0.6%, respectively (p<0.05). Aetiological evaluation revealed both transient hypothyroidism (33.3%) and permanent hypothyroidism (66.6%).Conclusion4.3% of babies born to hypothyroid mothers develop congenital hypothyroidism; aetiology being both transient and permanent. A venous test by 3 weeks is helpful in these babies to improve case identification.

scholarly journals The expression of microRNA-331-3p and microRNA-23b3 in Egyptian patients with early-stage hepatocellular carcinoma in hepatitis C-related liver cirrhosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Reham A. Aboelwafa ◽  
Walid Ismail Ellakany ◽  
Marwa A. Gamaleldin ◽  
Marwa A. Saad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis C ◽  
Early Stage ◽  
Group Iii ◽  
Real Time Quantitative Pcr ◽  
Early Stages ◽  
Group I ◽  
Egyptian Patients ◽  
Cirrhotic Patients

Abstract Background Hepatocellular carcinoma and hepatitis C are strongly associated. The current work aimed to study the expression levels of microRNA-331-3p and microRNA-23b-3p as propable biomarkers for detecting liver cancer (HCC) at its early stages in patients with HCV-related liver cirrhosis. The current prospective study included two hundred participants, divided into three groups: group I, 100 patients with HCV-related liver cirrhosis; group II, 50 HCC patients at early stages; and group III, 50 apparentlyhealthy controls. All patients had routine laboratory workup and ultrasound hepatic assessment. Values of microRNA-331-3p and microRNA-23b-3p were measured by real-time quantitative PCR. Results Levels of miR-331-3p were significantly higher in HCC patients than in cirrhotic patients and controls (p < 0.001), while levels of miR-23b-3p were significantly lower in HCC patients compared to cirrhotics and controls (p < 0.001). ROC curve revealed that miR-23b-3p had 80% sensitivity and 74% specificity, miR-331-3p had 66% sensitivity and 61% specificity, and AFP had 64% sensitivity and 61% specificity of 61% in discrimination between HCC patients from controls. Conclusion Serum miR-23b-3p is a more effective predictor than miR-331-3p and AFP for the development of hepatocellular carcinoma in hepatitis C (HCV)-related cirrhotic patients.

scholarly journals When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Katrin Schlie ◽  
Jaeline E. Spowart ◽  
Luke R. K. Hughson ◽  
Katelin N. Townsend ◽  
Julian J. Lum
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Patient Treatment ◽  
Low Oxygen ◽  
Tumor Environment ◽  
And Function ◽  
The Impact

Hypoxia is a signature feature of growing tumors. This cellular state creates an inhospitable condition that impedes the growth and function of all cells within the immediate and surrounding tumor microenvironment. To adapt to hypoxia, cells activate autophagy and undergo a metabolic shift increasing the cellular dependency on anaerobic metabolism. Autophagy upregulation in cancer cells liberates nutrients, decreases the buildup of reactive oxygen species, and aids in the clearance of misfolded proteins. Together, these features impart a survival advantage for cancer cells in the tumor microenvironment. This observation has led to intense research efforts focused on developing autophagy-modulating drugs for cancer patient treatment. However, other cells that infiltrate the tumor environment such as immune cells also encounter hypoxia likely resulting in hypoxia-induced autophagy. In light of the fact that autophagy is crucial for immune cell proliferation as well as their effector functions such as antigen presentation and T cell-mediated killing of tumor cells, anticancer treatment strategies based on autophagy modulation will need to consider the impact of autophagy on the immune system.

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