scholarly journals Beta-Thalassemia in Iran: New Insight into the Role of Genetic Admixture and Migration

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ali Reza Rezaee ◽  
Mohammad Mehdi Banoei ◽  
Elham Khalili ◽  
Massoud Houshmand
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Genetic Admixture ◽  
Beta Thalassemia ◽  
The Caspian Sea ◽  
Genetic Classification ◽  
And Migration ◽  
The Persian Gulf

Iran with an area of 1.648 million km2is located between the Caspian Sea and the Persian Gulf. The Iranian population consists of multiethnic groups that have been influenced by various invasions and migration throughout history. Studies have revealed the presence of more than 47 differentβ-globin gene mutations responsible forβ-Thalassemia in Iran. This paper is an attempt to study the origin ofβ-Thalassemia mutations in different parts of Iran. Distribution ofβ-Thalassemia mutations in Iran shows different patterns in different areas.β-Thalassemia mutations have been a reflection of people and area in correlation with migration and origin of ancestors. We compared the frequencies ofβ-globin mutations in different regions of Iran with those derived from neighboring countries. The analysis provided evidence of complementary information about the genetic admixture and migration of some mutations, as well as the remarkable genetic classification of the Iranian people and ethnic groups.

scholarly journals Genetic and epigenetic mechanisms in the development of congenital heart diseases

2021 ◽  
Vol 4 (2) ◽  
pp. e000196
Author(s):  
Yue Wu ◽  
Xiaosi Jin ◽  
Yuhao Zhang ◽  
Jing Zheng ◽  
Rulai Yang
Keyword(s):  
Congenital Heart ◽  
Heart Diseases ◽  
Gene Mutations ◽  
Morbidity And Mortality ◽  
Molecular Medicine ◽  
Epigenetic Mechanisms ◽  
Epigenetic Factors ◽  
Near Future

Congenital heart disease (CHD) is the most common of congenital cardiovascular malformations associated with birth defects, and it results in significant morbidity and mortality worldwide. The classification of CHD is still elusive owing to the complex pathogenesis of CHD. Advances in molecular medicine have revealed the genetic basis of some heart anomalies. Genes associated with CHD might be modulated by various epigenetic factors. Thus, the genetic and epigenetic factors are gradually accepted as important triggers in the pathogenesis of CHD. However, few literatures have comprehensively elaborated the genetic and epigenetic mechanisms of CHD. This review focuses on the etiology of CHD from genetics and epigenetics to discuss the role of these factors in the development of CHD. The interactions between genetic and epigenetic in the pathogenesis of CHD are also elaborated. Chromosome abnormalities and gene mutations in genetics, and DNA methylations, histone modifications and on-coding RNAs in epigenetics are summarized in detail. We hope the summative knowledge of these etiologies may be useful for improved diagnosis and further elucidation of CHD so that morbidity and mortality of children with CHD can be reduced in the near future.

scholarly journals Beta-Thalassemia Intermedia: A Single Thalassemia Center Experience from Northeastern Iraq

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Shaema Salih Amin ◽  
Sana Dlawar Jalal ◽  
Kosar Muhammed Ali ◽  
Ali Ibrahim Mohammed ◽  
Luqman Khalid Rasool ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Beta Thalassemia ◽  
Abnormal Liver Function Test ◽  
Hybridization Technique ◽  
Genetic Modifiers ◽  
Thalassemia Intermedia ◽  
Female Sex ◽  
Increased Risk ◽  
Thalassemia Mutation

Objective. To determine the molecular characterization and disease-associated complications of beta-thalassemia intermedia (β-TI) patients in Sulaymaniyah province, northeastern Iraq. Methods. A total of 159 β-TI patients from 114 families were enrolled. Detection of β-thalassemia mutations was done by reverse hybridization technique and direct gene sequencing. Also, the clinical and hematological data were collected through an electronic-based medical recording system using a designed comprehensive questionnaire. Results. Nineteen different β-globin gene mutations arranged in 37 various genotypes were determined. The most frequent were IVS-II-I (G>A) (47.2%), followed by IVS-I-6 (T>C) (23.3%) and IVS-I-110 (G>A) (5%). Among disease-related morbidities documented, bone disease amounted to 53% (facial deformity and osteoporosis), followed by endocrinopathies 17.6% (growth retardation and subclinical hypothyroidism), cholelithiasis 13.8%, pulmonary hypertension 11.3%, and abnormal liver function test 7.5%, whereas venous thrombosis, extramedullary hemopoiesis, and leg ulcer were less frequently observed. Age≥35 and female sex were risk factors for cholelithiasis, while age was an independent risk for hypothyroidism and female sex was associated with increased risk for osteoporosis. Mean serum ferritin of ≥1000 μg/L was associated with an increased risk of osteoporosis, whereas chelation therapy was protective for a multitude of other complications. Transfusion, on the other hand, increased the risk of osteoporosis, yet it was protective for cholelithiasis and hypothyroidism. Moreover, splenectomy was protective for cholelithiasis, although it was an independent risk for hypothyroidism. Finally, hydroxyurea was associated with an increased risk of osteoporosis, while it was protective for cholelithiasis. Discussion and Conclusion. β+-thalassemia mutation had contributed to 41.25 of families with a less severe β-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of β-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.

scholarly journals A reflection on the role of genetics in the concept of “epileptic encephalopathy”, as emerged from the most recent ILEA classification of epilepsy

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Angelo Russo ◽  
Giuseppe Gobbi
Keyword(s):  
Gene Mutations ◽  
International Community ◽  
Epileptic Encephalopathy ◽  
Specific Gene ◽  
International League Against Epilepsy ◽  
Epileptic Encephalopathies ◽  
Epilepsy Classification ◽  
International League

AbstractThe International League Against Epilepsy (ILAE) has been working to standardize the epilepsy classifications for over a hundred years.The latest epilepsy classification has been recently carried out with a careful overview on several topics including the “epileptic encephalopathies” concept and several constructive discussions on this topic have taken place in the international community of epileptologists.Here we wish to share our reflection on a statement of the ILAE commission on the “epileptic encephalopathy” concept, which in our opinion pays less attention to the “electroclinical syndromes” concept in favor of the new and very rapid genetic advances, thus generating confusion.Our aim is both to preserve the role of electroclinical syndromes, while allowing for the association of the phenotype with specific gene mutations, and to underline the importance of bringing electroclinical syndromes back to the forefront of epileptology.We believe the “match” is still open and for this reason we would like to share our considerations and to open a constructive debate on the “epileptic encephalopathy” concept.

scholarly journals Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents

2021 ◽  
Vol 8 (4) ◽  
pp. 233-247
Author(s):  
Bhuvana Selvaraj ◽  
◽  
Sangeetha Soundararajan ◽  
Shettu Narayanasamy ◽  
Ganesan Subramanian ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Globin Gene ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Thalassemia Major ◽  
Organ Damage ◽  
Beta Thalassemia ◽  
Hemochromatosis Gene

<abstract> <p>Hereditary Hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism associated with <italic>HFE</italic> gene mutations, characterized by increased iron absorption and accumulation leading to multi-organ damage caused by iron overload toxicity. Beta thalassemia is caused by a mutation in the human beta globin gene. Imbalanced production of globin chain results in beta thalassemia, where the unpaired alpha chains precipitates in red cell precursors leading to ineffective erythropoiesis and reduced RBC survival. Both HH and beta thalassemia condition results in rapid accumulation of iron lead to iron overload in tissues and organs. The study aims to analyze the frequency of <italic>HFE</italic> variants among beta thalassemia cases and their effect on iron overload. The frequency of three <italic>HFE</italic> variants C282Y, H63D, S65C was analyzed by PCR RFLP method among Beta Thalassemia Trait (BTT) (n = 203), Beta Thalassemia Major (BTM) (n = 19) and age and sex-matched control samples (n = 200). The present study furnished allele frequency of H63D variant in BTT, BTM and controls 8.13, 15.8 and 6% respectively. Ten out of 33 heterozygous H63D variants exhibited iron overload with higher ferritin levels indicating <italic>HFE</italic> variant might aggravate the absorption of iron. The C282Y variant was present in heterozygous state in 1 case among beta thalassemia carriers. The C282Y variant was absent among BTM and control cases. S65C <italic>HFE</italic> variant was absent in the present study. Iron overload was completely absent in the control cases among all three <italic>HFE</italic> genotypes. Hence it is inferred from the present investigation, analysis of <italic>HFE</italic> genes and iron status will remarkably help to reason out the probable reason behind the iron status and support in proper management of beta thalassemia cases.</p> </abstract>

scholarly journals Analysis of beta globin gene mutations in Diyarbakir

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Selahaddin Tekeş ◽  
Diclehan Oral ◽  
Murat Söker ◽  
Selda Şimşek ◽  
Veysiye Hülya Uzel ◽  
...  
Keyword(s):  
Globin Gene ◽  
Molecular Genetic ◽  
Point Mutations ◽  
Gene Mutations ◽  
Turkish Population ◽  
University Hospital ◽  
Beta Thalassemia ◽  
Amplification Refractory Mutation System ◽  
Compound Heterozygous ◽  
Common Mutation

Abstract Objectives Hemoglobin disorders are quite heterogeneous in the Turkish population. Up to now, more than forty different beta thalassemia mutations and 60 hemoglobin variants have been characterized in the country. The aim of this study was to investigate genetic heterogeneity of HBB gene mutations in patients and their parents at Southeastern Anatolia in Turkey. Methods Genomic DNA was isolated from 145 thalassemic patients’ blood samples and their parents in this study. Ten different HBB gene mutations HBB:c.-80T>A, HBB:c.17_18delCT, HBB:c.25_26delAA, HBB:c.92+1G>A, HBB:c.92+5G>C, HBB:c.92+6T>C, HBB:c.93-21G>A, HBB:c.135delC, HBB:c.315+1G>A, HBB:c.316-106C>G were screened by amplification refractory mutation system. Four Hb variants and some rare beta thalassemia mutation were characterized by DNA sequencing. Results In this study, 97 homozygous and 48 compound heterozygous thalassemic patients were diagnosed by molecular genetic analyses. As a results, 18 β-thalassemia mutations and four abnormal hemoglobins; HBB:c.20A>T, HBB:c.364G>C, HBB:c.34G>A and HBB:c.208G>A were detected at Dicle University Hospital. Conclusions In the results, HBB:c.93-21G>A is the most common mutation in the region. Three mutations [(HBB:c.93-21G>A), (HBB:c.25_26delAA) and (HBB:c.135delC)] account for about 58 per cent of all the point mutations. Except HBB:c.20A>T and HBB:c.364G>C, two silent Hb variants (HBB:c.34G>A and HBB:c.208G>A) were detected in this study. Hb Hamilton [β11 (GTT>ATT) Val>Ile] was seen first time in Turkey.

scholarly journals Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nur-Aisyah Aziz ◽  
Wan-Rohani Wan Taib ◽  
Nur-Khairunnisa Kharolazaman ◽  
Imilia Ismail ◽  
Hamid Ali Nagi Al-Jamal ◽  
...  
Keyword(s):  
Association Analysis ◽  
Globin Gene ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Haplotype Association ◽  
Malaysian Population ◽  
Archived Samples ◽  
Potential Use ◽  
Online Software

AbstractThis study sought to determine the potential role of HBB haplotypes to predict beta-thalassemia in the Malaysian population. A total of 543 archived samples were selected for this study. Five tagging SNPs in the beta-globin gene (HBB; NG_000007.3) were analyzed for SNP-based and haplotype association using SHEsis online software. Single-SNP-based association analysis showed three SNPs have a statistically significant association with beta-thalassemia. When Bonferroni correction was applied, four SNPs were found statistically significant with beta-thalassemia; IVS2-74T>G (padj = 0.047), IVS2-16G>C (padj = 0.017), IVS2-666C>T (padj = 0.017) and 3’UTR + 314G>A (padj = 0.002). However, 3'UTR + 233G>C did not yield a significant association with padj value = 0.076. Further investigation using combined five SNPs for haplotype association analysis revealed three susceptible haplotypes with significant p values of which, haplotypes 1-2-2-1-1 (p = 6.49 × 10−7, OR = 10.371 [3.345–32.148]), 1-2-1-1-1 (p = 0.009, OR = 1.423 [1.095–1.850] and 1-1-1-1-1 (p = 1.39 × 10−4, OR = 10.221 [2.345–44.555]). Three haplotypes showed protective effect with significant p value of which, 2-2-1-1-1 (p = 0.006, OR = 0.668 [0.500–0.893]), 1-1-2-2-1 (p = 0.013, OR = 0.357 [0.153–0.830]) and 1-1-2-1-1 (p = 0.033, OR = 0.745 [0.567–0.977]). This study has identified the potential use of intragenic polymorphic markers in the HBB gene, which were significantly associated with beta-thalassemia. Combining these five SNPs defined a new haplotype model for beta-thalassemia and further evaluation for predicting severity in beta-thalassemia.

scholarly journals Enhancer-dependent transcription of the epsilon-globin promoter requires promoter-bound GATA-1 and enhancer-bound AP-1/NF-E2.

1993 ◽  
Vol 13 (2) ◽  
pp. 911-917 ◽  
Author(s):  
Q Gong ◽  
A Dean
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
In Vitro Transcription ◽  
Beta Globin ◽  
Hypersensitive Site ◽  
Dnase Hypersensitive Site ◽  
Globin Promoter ◽  
Distal Promoter

We analyzed epsilon-globin transcription in erythroid cells and in erythroid extracts to determine the requirements for enhancer-dependent expression of this gene. Mutations that abolished GATA-1 binding at a single position in the promoter prevented interaction with enhancers, whereas elimination of a second more distal promoter GATA-1 site had no effect. Deletion or mutation of the GATA-1 sites in either the human beta-globin locus control region DNase-hypersensitive site II enhancer or the chicken beta A/epsilon-globin enhancer did not diminish the ability of the enhancers to interact with the promoter. In contrast, mutation of the AP-1/NF-E2 sites in these enhancers resulted in elimination of enhancement. In vitro transcription of these constructs was promoter dependent and was not sensitive to abolition of GATA-1 binding in the promoter, consistent with the role of GATA-1 solely as a mediator of the enhancer effect. Thus, GATA-1 regulates the response of the epsilon-globin gene to enhancers through a specific site in the promoter and requires enhancer AP-1/NF-E2 binding to transduce the enhancer effect on transcription.

Investigation of beta globin gene mutations in Syrian refugee patients with thalassemia major

2019 ◽  
Vol 44 (2) ◽  
pp. 126-129
Author(s):  
Hatice Çevirici ◽  
Can Acıpayam ◽  
Ebru Dündar Yenilmez ◽  
Fatma Burcu Belen ◽  
Esra Pekpak ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Amplification Refractory Mutation System ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Beta Thalassemia Major ◽  
Mutation System

Abstract Objectives This study, detection of beta globin gene mutations in thalassemia major patients who migrated from Syria to Kahramanmaraş region were planned. Materials and methods The study included 35 Syrian national beta thalassemia major patients. Beta globin gene mutations were detected by ARMS (Amplification Refractory Mutation System) method, RFLP (Restriction Fragment Length Polymorphism) method and DNA sequence analysis. Codon 15, codon 9/10, codon 5 and codon 8 mutations, which we could not detect with other methods in our study, were detected by sequence analysis. Results In beta thalassemia major patients, 16 types of mutations were detected, the most common being IVS-I-110 (n=8). Other mutations are according to frequency order IVS-II-745 (n=3), codon 44 (n=3), codon 15 (n=3), IVS-I-110/IVS-I-1 (n=3), codon 5 (n=2), IVS-I-1 (n=2), codon 8/IVS-II-1 (n=2), codon 44/codon 15 (n=2), IVS-II-1 (n=1), codon 39 (n=1), IVS-I-6/codon 5 (n=1), codon 9/10 (n=1), IVS-I-110/codon 39 (n=1), IVS-I-5/IVS-II-1 (n=1), codon 39/IVS-II-745 (n=1). Conclusions According to the results of our study beta-thalassemia mutations in Syrian immigrant groups show heterogeneity and mutation types of mutation map is similar to Turkey. The conclusion is to prevent families to have a second patient child by genetic counseling.

scholarly journals Beta-globin gene mutations in children with beta-thalassemia major from Sanliurfa province, Turkey

2011 ◽  
Vol 2011 (4) ◽  
pp. 264-268 ◽  
Author(s):  
Ali Aycicek ◽  
Ahmet Koc ◽  
Zeynep Canan Ozdemir ◽  
Hasan Bilinc ◽  
Abdurrahim Kocyigit ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Beta Thalassemia Major
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