scholarly journals Prevalence and Molecular Spectrum of α- and β-Globin Gene Mutations in Hainan, China

2020 ◽  
Author(s):  
Zhen Wang ◽  
Wenye Sun ◽  
Huaye Chen ◽  
Yongfang Zhang ◽  
Fei Wang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Minority Groups ◽  
Single Gene ◽  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Common Mutation ◽  
Hainan Province ◽  
Clinical Genetic ◽  
Fetal Cord Blood

Abstract Background: Thalassemia is one of the most prevalent inherited single gene diseases. Prevention of β-thalassemia through prenatal diagnosis is the one of the most effective and direct approach to control the spread of this life-threatening disease. This study aims to determine the prenatal diagnosis of α-thalassemia and β-thalassemia in 3049 families among eighteen regions of Hainan Province using molecular diagnosis.Methods: This study enrolled a total of 3049 couples and their fetuses at The First Affiliated Hospital of Hainan Medical University from January 2004 to March 2020. Genomic DNA was extracted from peripheral blood of the couples and villus, amniotic fluid, or fetal cord blood of fetuses. DNA-based diagnosis was performed using polymerase chain reaction. Results: Here, the most commonly detected mutation of α-thalassemia was a South-East Asian deletion (31.53%), followed by –α4.2/αα (11.15%), –α3.7/αα (11.02%). The most common mutation for β-thalassemia was CD41/42, followed by -28, accounting for 30.27% and 2.56%, respectively. The regions with the highest prevalence were the coastal regions and the regions with the lowest prevalence were Wenchang, Lingao and Ding’an. We also examined thalassemia gene mutations in Han people and other minority groups and found that the most common gene mutations in different ethnic were not homogeneous. Prenatal diagnosis showed 556 normal, 118 α-thalassemia hydrops and 161 β-thalassemia major fetuses. Conclusion: Our findings provide important information for clinical genetic counseling of prenatal diagnosis for thalassemia major in Hainan Province.

scholarly journals SPECTRUM OF BETA GLOBIN GENE MUTATIONS IN EGYPTIAN CHILDREN WITH β- THALASSEMIA

2014 ◽  
Vol 6 (1) ◽  
pp. e2014071 ◽  
Author(s):  
MR El-Shanshory ◽  
Adel Abd Elhaleim Hagag
Keyword(s):  
Dna Sequencing ◽  
Blood Count ◽  
Complete Blood Count ◽  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Direct Dna Sequencing ◽  
Rare Mutations ◽  
Egyptian Children

Background: The molecular defects resulting in β-thalassemia phenotype, in the Egyptian population show a clear heterogenic mutations pattern. PCR based techniques, including direct DNA sequencing are effective on the molecular detection and characterization of these mutations. The molecular characterization of β-thalassemia is absolutely necessary for carrier screening, for genetic counseling, and to offer prenatal diagnosis.The aim of the work: was to evaluate the different β-globin gene mutations in one hundred Egyptian children with β-thalassemia. Patients and Methods: One hundred of β-thalassemic Egyptian children, covering most Egyptian Governorates. All patients were subjected to meticulous history taking, clinical examinations, complete blood count, complete blood count, hemoglobin electrophoresis, serum ferritin and direct fluorescent DNA sequencing of β-globin gene to detect the frequency of different mutations in studied patients. Results: The most common mutations among patients were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A)19%,IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%, codon"Cd"39(C> T) 4%,-87(C>G) 3% and the rare mutations were: Cd37 (G>A), Cd8 (-AA), Cd29(-G), Cd5 (-CT), Cd6(-A), Cd8/9(+G), Cd 106/107(+G), Cd27(C>T), IVS II-16(G> C), Cd 28 (-C), Cap+1(A>C), -88(C>A), all of these rare mutations were present in 1%. There was considerable variation in phenotypic severity among patients resulting from interaction of different β° and β+mutations, 79(79%) patients were thalassemia major (TM) and 21(21%) were thassemia intermedia (TI), without genotype phenotype association. Conclusion: Direct DNA sequencing provides insights for the frequency of different mutations in β- thalassemic patients including rare and /or unknown ones.

scholarly journals BETA-GLOBIN GENE MUTATIONS IN TURKISH CHILDREN WITH BETA-THALASSEMIA: RESULTS FROM A SINGLE CENTER STUDY

2013 ◽  
Vol 5 (1) ◽  
pp. e2013055 ◽  
Author(s):  
Ali Fettah ◽  
Cengiz Bayram ◽  
Nese Yarali ◽  
Pamir Isik ◽  
Abdurrahman Kara ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Thalassemia Intermedia ◽  
Turkish Children ◽  
Tertiary Center

Introduction: The beta thalassemias are common genetic disorders in Turkey and in this retrospective study our aim was to evaluate β-globin chain mutations and the phenotypic severity of β-thalassemia patients followed-up in our hospital, a tertiary center which serves patients from all regions of Turkey. Materials and Methods: 106 pediatric patients were analysed for β-globin gene mutations by using DNA analysis. Patients were classified as having β-thalassemia major or β-thalassemia intermedia based on age at diagnosis, transfusion frequency and lowest hemoglobin concentration in between transfusions. Results: There were 106 patients (52.8% female and 47.2% male) with a mean age of 11.2±5 years (1.6 – 22.3 years). Eighty-four (79.2%) patients had β-thalassemia major, whereas the remaining 22 patients (20.8%) were identified as having β-thalassemia intermedia. Overall, 18 different mutations were detected on 212 alleles. The most frequently encountered mutation was IVS I.110 (G>A) (35.3%), followed by Codon 8 del-AA (10.4%), IVS II.1 (G>A) (8%), IVS I.1 (G>A) (7.5%), Codon 39 (C>T) (7.1%) and Codon 5 (-CT) (6.6%), which made up 79.4% of observed mutations. According to present results, IVS I.110 (G>AA) was the most frequent mutation observed in this study, as in other results from Turkey. Evaluation of β-thalassemia mutations in 106 patients with 212 alleles, revealed the presence of homozygous mutation in 85 patients (80.2%) and compound heterozygous mutation in 21 patients (19.8%). The mutations detected in patients with homozygous mutation were IVS I.110 (G>A) (38.8%), Codon 8 del –AA (11.8%), IVS II.1 (G>A) (8.2%) and IVS I.1 (G>A) (8.2%). Observed mutations in the compound heterozygotes were Codon 39 (C>T)/Codon 41-42 (-CTTT) (14.3%), IVS I.110 (G>A)/Codon 39(C>T) (14.3%), IVS I.110 (G>A)/Codon 44(-C) (14.3%), and IVS II.745 (C>G)/ 5’UTR + 22 (G>A) (9.5%). Conclusion: Our hospital is a tertiary referral center that provides care to patients from all over the country, and thus the distribution of mutations observed in the current study is significant in term of representing that of the country as a whole.

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.

The Spectrum of δ-Thalassemia in the Western Sicily.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3824-3824
Author(s):  
Aurelio Maggio ◽  
Cristina Passarello ◽  
Gaetano Ruggeri ◽  
Pietro Teresi ◽  
Maurizio Anzà ◽  
...  
Keyword(s):  
Globin Gene ◽  
Point Mutations ◽  
Gene Mutations ◽  
Common Mutation ◽  
Gene Variants ◽  
Three Samples ◽  
Western Sicily ◽  
Gene Defects ◽  
Correct Estimation ◽  
Sicilian Population

Abstract The detection of β-thalassemia carriers is based on the correct estimation of HbA2 values.The diagnosis of β-thalassemia carriers may be more complicated in presence of δ-thalassemia because the interaction between δ and β-globin gene defects modifies the HbA2 values. For this reason, we studied the spectrum of δ-globin gene mutations present in the Sicilian population, characterized by its very high heterogeneity in β-thalassemia genotype and phenotype. The samples were selected by screening and routine prenatal diagnoses counseling for thalassemia. Among 7153 samples studied for β-thalassemia, 205 samples were selected for HbA2 levels ranging from 0.5% to 2.0% and normal haematology parameters, suspected of being δ-thal carriers in the absence of α and β-thalassemia or hemoglobin variants, and for HbA2 levels from 2.1% to 4.6% in subjects suspected of compound heterozygotes for δ and β-thalassemia and between 1.4% and 2.0% for δ and α-thalassemia. We have considered the value of 2% as the treshold between normal and d-carrier subjects. One-hundred-eighty-three samples showed to be positive for δ-globin gene mutations.Twelve mutations were detected and among these five were new δ-globin gene defects (HbA2-Catania, HbA2-Corleone, HbA2-Ventimiglia; HbA2-Montechiaro and HbA2-Bagheria) determining δ-globin gene variants and seven were already described mutations. Among these six of them were point mutations (HbA2-Mitsero, HbA2-NYU,HbA2-Yialousa, HbA2-Coburg, HbA2-Fitzroy) and one a 7.2 Kb deletion mutation known as the δ-Corfù type, HBD g.5946_1262del. As it was previously shown in Sicily for β-thalassemia, only three mutations account for 91% (HbA2-Yialousa, HbA2-NYU, IVS II-3′ A→G) of the overall δ-globin gene defects. HbA2-Yialousa (g.82G→T) is the most common mutation found in Sicilian population (81%) while the other eleven mutations are less frequent between 0.5 to 5.5%. These findings suggest that in Sicily δ-thalassemia is very common (2.5%) and as it was described, previously, for the β-thalassemia mutations,this also is very heterogeneous (twelve mutations). This information is noteworthy considering the implication that the interaction between β and δ-thalassemia could determine in terms of HbA2 decrease in subjects heterozygotes for β-thalassemia. HbA2 levels in δ-thalassemia and δ globin gene variants with and without interaction with α or β-globin gene mutations. The δ-alleles are all in heterozygote state except three cases with homozygosis. βA/βA αα/αα Gγ-158/Gγ 1.1 1 βA/βA αα/αα 1.7±0.2 113 βA/βA αα/αα 2.1±0.1 4 βA/βA αα/αα 0.7±0.1 3 βA/β(IVS1,110) αα/αα 3.35±0.15 2 βA/β(cd39) αα/αα 3.5 1 Hb A2-Yialousa βA/β(IVS1,1) αα/αα 3.5 1 βA/β(−87G) αα/αα 4.6 1 βA/β(−101) αα/αα 2.8 1 βA/β(IVS1,6) αα/αα 3.0±0.2 4 βA/βS αα/αα 2.7±0.1 5 βA/βA α−3.7α/αα 1.8±0.2 5 βA/βA α−20.5α/αα 1.4±0.1 2 βA/βA α−Medα/αα 1.6±0.1 2 βA/βA αNcoIα/αα 1.7±0.2 2 βA/βA αHphIα/αα 1.7±0.2 2 Hb A2-NYU βA/βA αα/αα 1.5±0.2 9 βA/β(Valletta) α−3.7α/αα 1.6 1 Hb A2-Mitsero βA/βA αα/αα 1.9±0.2 3 βA/βA α−3.7α/αα 1.6 1 Hb A2-Coburg βA/βA αα/αα 1 1 Hb A2-Fitzroy βA/βA αα/αα 1.4±0.2 3 Hb A2-Catania βA/βA αα/αα 1.2 1 Hb A2-Corleone βA/βA αα/αα 1.6 1 Hb A2-Ventimiglia βA/βA αα/αα 2 1 Hb A2-Montechiaro βA/βA αα/αα 1.3 1 Hb A2-Bagheria βA/βA αα/αα 1.7 1 7.2 Kb deletion βA/βA αα/αα 1.4±0.1 3 βA/βA αα/αα 1.5±0.2 4 IVS II-3′ βA/β(IVS1,110) αα/αα 3.3±0.2 3 βA/β αα/ααα 2.5 1 GENOTYPE δ GENOTYPEβ GENOTYPEα GENOTYPEγ HbA2% N° OF δ CARRIERS

scholarly journals Detection of Rare Beta Globin Gene Mutation [+22 5UTR(G>A)] in an Infant, Despite Prenatal Screening

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Mohammad Reza Mahdavi ◽  
Hosein Karami ◽  
Mohammad Taghi Akbari ◽  
Hosein Jalali ◽  
Payam Roshan
Keyword(s):  
Prenatal Screening ◽  
Married Couple ◽  
Globin Gene ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Common Mutation ◽  
Screening Programs ◽  
Rare Mutations ◽  
Hereditary Disorders ◽  
Screening And Diagnosis

Background. Beta thalassemia is one of the most common hereditary disorders worldwide. In Iran, it is frequently reported from northern and southern provinces. In order to prevent child birth to be affected by this complication, prenatal screening and diagnosis are carried out nationwide. However, in some instances, this program is unable to identify rare mutations leading to thalassemia.Case Presentation. A married couple, who took part in prenatal screening and diagnosis, gave birth to a child who is affected by thalassemia major. After several molecular examinations, a rare mutation [+22 5UTR (G>A)] in compound heterozygote state along with a common mutation [codon 8 (-AA)] was found.Conclusion. This case study suggests that more advanced molecular evaluations must be integrated in prenatal screening programs to identify rare mutations and antenatal diagnosis of thalassemia cases.

scholarly journals β globin mutations in Turkish, Northern Iraqi and Albanian patients with β thalassemia major

2018 ◽  
Vol 8 (2) ◽  
Author(s):  
Veysel Sabri Hancer ◽  
Tunc Fisgin ◽  
Murat Buyukdogan ◽  
Ceyhun Bozkurt ◽  
Sotiraq Lako
Keyword(s):  
Genetic Counseling ◽  
Genomic Dna ◽  
Mutation Detection ◽  
Globin Gene ◽  
Venous Blood ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Target Dna ◽  
Frequent Allele ◽  
Pcr Genotyping

The mutation detection of β thalassemia is absolutely necessary for molecular diagnosis, as well as any genetic epidemiological study. The β globin gene has 3 exons and 2 introns, involved in β-thalassemic pathogenesis. The study aim of the study is to characterize the spectrum of β globin gene mutations in 136 Turkish, Northern Iraqi and Albanian pediatric β thalassemia major patients. After genomic DNA extraction from venous blood and amplification of the target DNA regions with PCR, genotyping was achieved by Sanger based DNA sequencing. The IVSI-110 G>A mutation was the most frequent allele in the Turkish and Albanian patients. In Northern Iraqi patients IVSI-1 G>A was is the most frequent. There are two mutations are firstly reported for Albania [c.*111 A>G 3’ UTR (rs63751128) and c.113 G>A (p.Trp38Ter, p.W38*) (rs35887507)] with this study. These findings may be of value for genetic counseling, premarital diagnosis, prenatal diagnosis and prevention programs.

Status research Thalassemia carier among children of ethnic Tay, Dao in Tuyen Quang province

2021 ◽  
Vol 05 (03) ◽  
pp. 102-109
Author(s):  
Thi Thu Giang Do ◽  
◽  
Quang Thanh Pham ◽  
Phuong Thuy Ho
Keyword(s):  
Ethnic Minority ◽  
Dna Analysis ◽  
Single Gene ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Gene Mutations ◽  
Screening Tests ◽  
Minority Children ◽  
Alpha Globin ◽  
Ethnic Minority Children

Objectives: To determine the prevalence of thalassemia carrier, genotype and hematological parameters among children bearing the thalassemia gene in Tuyen Quang. Methodology: A descriptive study was conducted from January to March 2017. 505 ethnic minority children in 6 districts and Tuyen Quang City, Tuyen Quang province were registered voluntarily by the family in the study. MCV index <80fL combined with the DCIP test were used for screening thalassemia and HbE. Hemoglobin electrophoresis and DNA analysis of mutations in the globin alpha gene was performed for all cases positive with screening tests. Results: The prevalence of thalassemia common for ethnic minority children in Tuyen Quang was 28,1%. Four types of single-gene mutations in the alpha globin gene were identified, following types --SEA, -α3.7; -αCS; -α4.2. Conclusion: The general prevalence of thalassemia gene among the Tay and Dao children in Tuyen Quang is 28.1%. Six phenotypic groups carrying thalassemia gene were detected with 10 mutant genotypes. Mutation - SEA accounts for the highest proportion of single allele mutations (72.09%). Keywords: Thalassemia carrier, children, ethnic Tay, ethnic Dao, Tuyen Quang

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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