The Prevalence Of ?-Thalassemia Mutations in South Western Maharashtra.
ABSTRACT: Thalassemia has been recognized by the World Health Organization as important inherited disorders principally impacting on the populations of low income countries. In this report, the prevalence of common ?-thalassemia mutations in India was defined in 126 ?-thalassemia carrier subjects in a western Indian population mainly from the south-western Maharashtra. The six most common ?-thalassemia mutations were detected, which included IVS I-5 (G-C), IVS I-1 (G-T), codon 8-9 (+G), codon 41/42 (-TCTT), Codon 15 (G-A), and 619 bp deletion at 3' end of ?-globin gene. These mutations accounted for 93.66 % in 126 ?-thalassemia carrier subjects and 6.34 % remained uncharacterized. Out of 126, 82 (65.07 %) showed the most common (prevalent) type of mutation, IVS I-5 (G-C), followed by IVS I-1 (G-T) showed by 12 (9.52 %) subjects. Three (2.38 %) subjects showed 619 bp deletion, codon 8/9 (+G) and codon 15 (G-A) mutations were present in eight subjects each (6.34 %). Only five (3.96 %) subjects showed codon 41/42 (-TCTT). There were eight (6.34 %) subjects where mutation was not any of the six mutations studied. This study provides the pattern of ? thalassemia mutations from south-western Maharashtra, which will help to prevent ?-thalassemia using prenatal diagnosis and proper counseling.
Project description:<h4>Background</h4>Thalassemia is a group of inherited autosomal recessive hemolytic anemia disease caused by reduced or absent synthesis of globin chain/chains of hemoglobin. Only few studies showed the molecular characterization of α- and β-thalassemia in Meizhou city of China.<h4>Methods</h4>A total of 22,401 individuals were collected; hematological and hemoglobin electrophoresis analysis and thalassemia genetic testing were performed.<h4>Results</h4>Eleven thousand and thirty (49.24%) cases with microcytosis (mean corpuscular volume (MCV) < 82 fl), 11,074 (49.44%) cases with hypochromia (mean corpuscular Hb (MCH) < 27 pg) in 22,401 subjects, 11,085 cases with abnormal hemoglobin results were identified in subjects aged ≥6 months. 7,322 (32.69%) subjects harbored thalassemia mutations, including 4,841 (21.61%) subjects with α-thalassemia, 2,237 (9.99%) with β-thalassemia, and 244 (1.09%) with α-thalassemia combined β-thalassemia. 18 genotypes of α-thalassemia mutations and 27 genotypes of β-thalassemia mutations were characterized. The most frequent α gene mutation was --<sup>SEA</sup> (64.69%), followed by -α<sup>3.7</sup> (19.93%), -α<sup>4.2</sup> (7.73%), α<sup>CS</sup> α (3.97%), and α<sup>WS</sup> α (2.83%). The six most common β-thalassemia mutations were IVS-II-654 (C>T) (39.79%), CD41-42 (-TCTT) (33.02%), -28 (A>G) (10.38%), CD17 (A>T) (9.08%), CD27-28 (+C) (2.14%), and CD26 (G>A) (2.02%). In addition, MCV and MCH were sensitive markers for α- and β-thalassemia except for -α<sup>3.7</sup> /αα, -α<sup>4.2</sup> /αα, α<sup>CS</sup> α/αα, α<sup>WS</sup> α/αα, and β<sup>Cap+40-43</sup> /β<sup>N</sup> .<h4>Conclusions</h4>The --<sup>SEA</sup> , -α<sup>3.7</sup> , and -α<sup>4.2</sup> deletions were the main mutations of α-thalassemia, while IVS-II-654 (C>T), CD41-42 (-TCTT), -28 (A>G), and CD17 (A>T) mutations of β-thalassemia in Meizhou. There were some differences in thalassemia mutation frequencies in Meizhou city from other populations in China.
Project description:OBJECTIVE:The aim of the study was to explore genotype distribution thalassemia and G6PD deficiency in Meizhou city, China. METHODS:A total of 16 158 individuals were involved in thalassemia genetic testing. A total of 605 subjects were screened for common Chinese G6PD mutations by gene chip analysis. Genotypes and allele frequencies were analyzed. RESULTS:A total of 5463 cases carried thalassemia mutations were identified, including 3585 cases, 1701 cases, and 177 cases with ?-, ?-, and ? + ?-thalassemia mutations, respectively. --SEA (65.12%), -?3.7 (19.05%), and -?4.2 (8.05%) deletion were the main mutations of ?-thalassemia, while IVS-II-654(C ? T) (40.39%), CD41-42(-TCTT) (32.72%), -28(A ? G) (10.11%), and CD17(A ? T) (9.32%) mutations were the principal mutations of ?-thalassemia in Meizhou. There were significant differences in allele frequencies in some counties. Genetic testing for G6PD deficiency, six mutation sites, and one polymorphism were detected in our study. A total of 198 alleles with the mutation were detected among 805 alleles (24.6%). G6PD Canton (c.1376 G ? T) (45.96%), G6PD Kaiping (c.1388 G ? A) (39.39%), and G6PD Gaohe (c.95 A ? G) (9.09%) account for 94.44% mutations, followed by G6PD Chinese-5 (c.1024 C ? T) (4.04%), G6PD Viangchan (c.871G ? A) (1.01%), and G6PD Maewo (c.1360 C ? T) (0.51%). There were some differences of the distribution of G6PD mutations among eight counties in Meizhou. CONCLUSIONS:The --SEA , -?3.7 , and -?4.2 deletion were the main mutations of ?-thalassemia, while IVS-II-654(C ? T), CD41-42(-TCTT), -28(A ? G), and CD17(A ? T) mutations were the principal mutations of ?-thalassemia in Meizhou. G6PD c.1376 G ? T, c.1388 G ? A, and c.95 A ? G were the main mutations of G6PD deficiency. There were some differences of the distribution of thalassemia and G6PD mutations among eight counties in Meizhou.
Project description:Background:We aimed to investigate the molecular basis of ?-Thalassemia intermedia (TI) in the West Bank region and its management practices. Methods:This was a case series multi-center study and included 51 cases of TI. DNA sequencing was used to analyze ?-globin gene mutations. Common ?-globin gene mutations were screened by Gap-PCR (-?3.7, -?4.2, --MED, ???anti3.7) or DNA sequencing (?2-IVS II 5?nt del). XmnI -158 C?>?T polymorphisms of G?-globin gene was determined by RFLP-PCR. Results:Seven ?-globin gene mutations were observed, namely IVS-I -6 C?>?T, IVS-I-110?G?>?A, IVS-II-1?G?>?A, IVS-I-1?G?>?A, Codon 37 Trp?>?Stop, beta -?101 and IVS-II-848 C?>?A. Ten genotypes were observed. Homozygosity for IVS-I-6 accounted for the majority of TI cases with a frequency of 74.5%. The second common ?-globin gene genotype was homozygote IVS-I-110?G?>?A (5.8%) and homozygote IVS-II-1?G?>?A (5.8%). The remaining seven genotypes were each detected in about 2% of patients. ?-Thalassemia mutations were seen in five patients (9.8%), and included (-?3.7, ???anti3.7 and ?2-IVSII-5 nt del). XmnI polymorphism was observed in four patients (7.8%), three homozygotes and one heterozygote. Conclusions:Homozygosity for the mild ?-globin gene IVS-I-6 allele was the major contributing factor for the TI phenotype among the study subjects. The role of XmnI SNP and ?-thalassemia mutations in ameliorating the TI phenotype was observed in few patients for each factor. The beta -?101 C?>?T mutation was diagnosed in one patient in homozygote state for the first time in Palestine.
Project description:Hemoglobinopathies are major health problems among Iraqi Kurds, who are a distinct ethnic group inhabiting North and Northeastern Iraq. We reviewed published literature on these disorders in this part of the world, and it was revealed that the most prevalent is ?-thalassemia with carrier rates of 3.7-6.9%. Alpha thalassemia is less prevalent with carrier rates of 0.03-1.22%, while the sickle cell gene is variably distributed with carrier rates of 0.06-1.2%. Other structural hemoglobinopathies and ??-thalassemia are sporadic. Twenty-seven different ?-thalassemia mutations were identified, with seven constituting 82% of 1039 chromosomes characterized, namely: IVS-II-1 (G>A), IVS-I-6 (T>C), IVS-I-I (G>A), codon 8 (-AA), codon 8/9 (+G), IVS-I-110 (G>A), and codon 5 (-CT). There were notable regional variations in the distribution of ?-thalassemia mutations, with Cd44 being mainly prevalent in the North, while IVS-I-110 is mainly prevalent in the East. In relevance to ?-thalassemia, ten different mutations were detected, with the four most frequent constituting 92.4% of 262 alleles characterized being: -?<sup>3.7</sup>, --<sup>MED</sup>, ?<sup>-5nt</sup>?, and ?<sup>PolyA1</sup>?. In relevance to sickle cell gene, it is seen in the northern part of the region bordering Turkey, with comparable prevalence rates, and is associated, similar to Turkey, mainly with the Benin haplotype, unlike that in Southern Iraq where it is associated with the Arab-Indian haplotype, similar to Eastern Arabian Peninsula. Given the high prevalence of hemoglobinopathies in the region, and the high rates of consanguineous marriages, a preventive program was initiated in 2008, and results of its first 5 years were promising, though there are still many outstanding challenges that require addressing.
Project description:<b>Background:</b> Thalassemia is one of the most common genetic diseases in southern China. Howerver, population in different regions or different population has their own spectrums of thalassemia. To investigate the prevalence and spectrum features of thalassemia among children in Guangxi. Hematology and genetic analysis were performed on 71,459 children aged 1-10 years in various regions of Guangxi. <b>Results:</b> A total of 11,821 children were diagnoses with thalassemia including 7,615 (10.66%) subjects of α-thalassemia, 3,507 (4.90%) subjects of β-thalassemia, and 699 (0.98%) cases with both α- and β-thalassemia. Nine α-thalassemia mutations and 30 genotypes were identified among the α-thalassemia children. The - -<sup>SEA</sup> and - -<sup>SEA</sup>/αα were the most frequent mutation and genotype, respectively. One α-thalassemia fusion gene and a rare 2.4 kb deletion both causing α<sup>+</sup>-thalassemia were identified, respectively. Thirteen β-thalassemia mutations and 31 genotypes were characterized among the β-thalassemia children, with the most common mutation CD41-42 (-CTTT) accounting for 46.05% of the β-mutations. Two rare mutations IVS-II-5 (G>C), and IVS-I-2 (T>C) were firstly identified. Furthermore, 92 genotypes were identified among 699 children with both α- and β-thalassemia. <b>Conclusions:</b> Our findings highlight the great heterogeneity and the extensive spectrum of thalassemia among children in Guangxi, which provide an available reference for prevention of thalassemia in this area.
Project description:?-Thalassemias and abnormal hemoglobin variants are among the most common hereditary abnormalities in humans. Molecular characterization of the causative genetic variants is an essential part of the diagnostic process. In geographic areas with high hemoglobinopathy prevalence, such as the Mediterranean region, a limited number of genetic variants are responsible for the majority of hemoglobinopathy cases. Developing reliable, rapid and cost-effective mutation-specific molecular diagnostic assays targeting particular populations greatly facilitates routine hemoglobinopathy investigations. We developed a one-tube single-nucleotide primer extension assay for the detection of eight common Mediterranean ?-thalassemia mutations: Codon 5 (-CT); CCT(Pro)->C-, Codon 6 (-A); GAG(Glu)->G-G, Codon 8 (-AA); AAG(Lys)->-G, IVS-I-1 (G->A), IVS-I-6 (T->C), IVS-I-110 (G->A), Codon 39 (C->T), and IVS-II-745 (C->G), as well as the hemoglobin S variant beta 6(A3) Glu>Val. We validated the new assay using previously genotyped samples obtaining 100% agreement between independent genotyping methods. Our approach, applicable in a range of Mediterranean countries, offers a combination of high accuracy and rapidity exploiting standard techniques and widely available equipment. It can be further adapted to particular populations by including/excluding assayed mutations. We facilitate future modifications by providing detailed information on assay design.
Project description:Background and purpose:Thalassemia is a genetic disorder with a fairly high prevalence worldwide. Three to 10% of Indonesian people are estimated to be carriers for thalassemia. This study was intended to figure out the spectrum of genetic mutations of patients with thalassemia in Samarinda City, East Kalimantan. Methods:The research subjects consisted of 31 ?-thalassemia patients registered with the Association of Thalassemia Patients' Parents (POPTI) of Samarinda. DNAs were extracted from the patients' blood samples then amplified by the direct sequencing technique with polymerase chain reaction to analyze ?-globin gene mutations. Result:The study results show that the male/female ratio was 51.6%:48.4%, the patients' ages ranged from 4?years to 56?years with an average age of 14?years, and the dominant ethnic group was Javanese (64.5%). The DNA analysis yielded 7 types of mutant alleles, namely Cd26/HbE (GAG>AAG) at 48.4%, IVS-1-5 (G?>?C) at 14.5%, IVS-1-2 (T?>?C) at 12.9%, Cd35 (-C) at 8.1%, IVS-1-1 (G?>?T) at 6.5%, and, the least frequently encountered mutant alleles, Cd30 (AGG?>?ACG) and Cd60 (GTG?>?GAG) each at 3.2%. Conclusion:This study discovered unreported mutant in Indonesia, namely Cd60 (GTG?>?GAG).
Project description:Beta (?)-thalassemia is the most frequently observed hereditary blood disorder in the world. It is characterized by deficiency of hemoglobin ?-globin gene and is also a profoundly heterogeneous both at the molecular and clinical level. In the case of ?-thalassemia, there is reduced (?(+) type) or absent (?(o) type) synthesis of the beta chains of hemoglobin. ?-Thalassemia clinically occurs in three main forms: major, intermedia and minor according to requirement of transfusion. The objective of this study was to evaluate ?-thalassemia mutations in 89 patients ranging from 2 months to 16 years of age, who enrolled to Medical School Research and Training Hospital, Gaziantep University. The direct DNA sequence analysis was performed for mutation scanning of ?-globin gene. 89 children with ?-Thalassemia including all types were analyzed, 16 different ?-thalassemia mutations were detected. We have also identified a novel mutation (HBB.c.-80delT, rs397509430) in the promoter region (-30 TATA box) of ?-globin gene, and clinical data of patient having novel mutation was given. The ?-Thalassemia mutations were determined as ?-Thalassemia major type in 42 patients (47.19 %), ?-Thalassemia intermedia in 4 (4.49 %), ?-Thalassemia minor in 43, (48.31 %) patients. The most frequent mutation was IVS I-110 G>A, followed by IVS I-1 G>A, IVS I-6 T>C, IVS II-1 G>A, respectively.
Project description:?-Thalassemia (?-thal) is a major public health problem in Albania as it is in many Mediterranean countries. We determined the different ?-thal alleles that are present in the Albanian population by using the temporal temperature gradient electrophoresis (TTGE) method because of its high throughput, cost-effectiveness, sensitivity and simplicity. DNA from blood of 68 patients with ?-thal, 26 with sickle cell anemia or sickle cell ?-thal, 54 parents of these patients and 14 heterozygotes related to these families. We found the IVS-I-110 (G>A), codon 39 (C>T), IVS-I-6 (T>C), IVS-I-1 (G>A) and codon 44 (-C) mutations that accounted for nearly 90% of the ?-thal alleles. Their frequencies were similar to those found in other studies in the Albanian population. This method has permitted the detection of heterozygotes for ?-thal in this population and offers a prenatal diagnosis with a probability of 90% accuracy.
Project description:BACKGROUND:?-Thalassemia is rare in sub-Saharan Africa. Previous studies have suggested that it is limited to specific parts of West Africa. Based on hemoglobin A2 (HbA2 ) concentrations measured by HPLC, we recently speculated that ?-thalassemia might also be present on the East African coast of Kenya. Here, we follow this up using molecular methods. METHODS:We used raised hemoglobin A2 (HbA2 ) values (> 4.0% of total Hb) to target all HbAA members of a cohort study in Kilifi, Kenya, for HBB sequencing for ?-thalassemia (n = 99) together with a sample of HbAA subjects with lower HbA2 levels. Because HbA2 values are artifactually raised in subjects carrying sickle hemoglobin (HbS) we sequenced all participants with an HPLC pattern showing HbS without HbA (n = 116) and a sample with a pattern showing both HbA and HbS. RESULTS:Overall, we identified 83 carriers of four separate ?-thalassemia pathogenic variants: three ?0 -thalassemia [CD22 (GAA?TAA), initiation codon (ATG?ACG), and IVS1-3' end del 25bp] and one ?+ -thalassemia pathogenic variants (IVS-I-110 (G?A)). We estimated the minimum allele frequency of all variants combined within the study population at 0.3%. CONCLUSIONS:?-Thalassemia is present in Kilifi, Kenya, an observation that has implications for the diagnosis and clinical care of children from the East Africa region.